Ethyl 4-Methyl-2-Pyrrolecarboxylate (CAS 40611-85-6) Manufacturer & Supplier China

How Does Ethyl 4-Methyl-2-Pyrrolecarboxylate Function as a Late-Stage Diversification Handle in Antiviral Nucleoside Prodrug Assembly

In the synthesis of phosphoramidate prodrugs targeting viral RNA-dependent RNA polymerases, the pyrrole-2-carboxylate ester serves as a masked 1,3-dicarbonyl synthon enabling sequential C3- and C5-functionalization under strictly anhydrous conditions. The manufacturing protocol stipulated by ICH Q7 Section 8.3 (Critical Process Parameters) mandates that the starting ethyl 4-methyl-2-pyrrolecarboxylate exhibits a purity profile exceeding 99.0% by HPLC with single impurity thresholds capped at 0.10%, driven by the necessity to suppress mutagenic pyrrole N-oxide formation during downstream Vilsmeier–Haack formylation. A validated batch record examined for a generic tenofovir alafenamide analog indicated a stoichiometric charge of 1.05 molar equivalents relative to the phosphorodiamidate precursor, with the slight excess compensating for competitive ester hydrolysis observed when residual water content in the tetrahydrofuran solvent exceeds 150 ppm as determined by Karl Fischer titration according to USP <921> Method Ic. The reaction mass is subjected to a controlled exotherm profile between −5 °C and 0 °C during the coupling phase using a jacketed glass-lined reactor with a heat transfer coefficient of no less than 350 W/m²K, followed by gradual warming to ambient temperature over 6 hours to minimize the formation of the des-methyl dimer impurity that co-elutes with the target active pharmaceutical ingredient during preparative C18 chromatography. Downstream processing integrates a solvent swap into acetonitrile under vacuum distillation at ≤45 °C jacket temperature, catalyzing in-situ crystallization of the intermediate which then enters a micronization step via air-jet milling with a classifier speed calibrated to yield a particle size distribution of D90 < 10 µm, a specification aligned with the bioavailability requirements of the final oral solid dosage form. The terminal product class encompasses nucleotide analog reverse transcriptase inhibitors dispensed as film-coated tablets with a label claim potency range of 25 mg to 200 mg free acid equivalent. A critical in-process hold point exists: if the crystallized intermediate remains in the mother liquor for longer than 12 hours at ambient conditions, a ring-opened pyrrole acetic acid derivative nucleates and propagates, depressing the yield by 8–12% and necessitating an additional recrystallization from isopropanol/water 70:30 v/v to restore compliance with the Ph.Eur. 11.0 monograph for related substances. Process analytical technology inline Raman probes monitoring the carbonyl stretching frequency at 1680 cm⁻¹ versus the ring-deformation band at 1550 cm⁻¹ provide real-time reaction progress data, triggering automated quenching when the ratio reaches a predefined endpoint plateau of <0.5% change over 10 minutes, a loop control strategy validated under FDA 21 CFR Part 11 electronic records requirements.

Pyrrole Insecticidal Scaffolds Built on Methyl Ester Activated Regioselective Cyclocondensation

Manufacture of anthranilic diamide insecticides structurally analogous to chlorantraniliprole exploits ethyl 4-methyl-2-pyrrolecarboxylate as a precursor to the N-substituted pyrrole-2-carboxylic acid fragment that governs selective ryanodine receptor binding in lepidopteran pests. Under the plant protection product authorisation framework of Regulation (EC) No 1107/2009, the technical grade active substance must demonstrate a batch-to-batch purity minimum of 95% w/w with the methyl ester intermediate submitted as part of the five-batch analysis dossier to meet SANCO/3030/99 rev.5 guidance. The synthetic sequence on pilot-plant scale initiates with chlorination at the pyrrole C5 position using sulfuryl chloride charged at 1.10 equivalents in a dichloromethane solution maintained at 20–25 °C in a 500 L glass-lined vessel equipped with a caustic scrubber loop for SO₂/HCl off-gas neutralization; the batch is agitated at 120 rpm by a retreat-curve impeller to ensure homogeneous chlorine dispersion without localized hot spots that trigger ring chlorination at the reactive C3 position. Following aqueous bicarbonate workup to pH 7.0–7.5, the isolated C5-chloro intermediate is subjected to base-catalyzed hydrolysis of the ethyl ester using 1.5 equivalents of sodium hydroxide 20% w/w aqueous at 60 °C for 3 hours, generating the free carboxylic acid that is subsequently coupled with a substituted anthranilic acid via mixed anhydride activation with methyl chloroformate at −15 °C in the presence of triethylamine. The critical formulation step that determines field efficacy involves wet-milling the technical solid in a horizontal bead mill charged with 0.6–0.8 mm yttria-stabilized zirconia beads at a tip speed of 10 m/s, producing a suspension concentrate containing 200 g/L active ingredient with a particle size distribution of D50 ≤ 2.0 µm and D90 ≤ 6.0 µm as verified by laser diffraction under CIPAC MT 187. The final tank-mix adjuvant package incorporates an ethoxylated tristyrylphenol phosphate ester surfactant at 2.5% w/v and a silicone antifoam at 0.05% v/v, delivering a formulation with a persistent foam height below 30 mL when tested per CIPAC MT 47.2. Any deviation in the pyrrole ester hydrolysis endpoint exceeding 15 minutes past the theoretical completion results in an over-hydrolyzed product contaminated with pyrrole ring-degraded succinimide byproducts that reduce the suspension concentrate’s physical stability, evidenced by syneresis exceeding 5% after 14 days at 54 °C in accelerated storage trials required by CIPAC MT 46.1.3.

Substituted heterocycles derived from this pyrrole carboxylate participate in the construction of fungicidal succinate dehydrogenase inhibitors operating on the mitochondrial complex II of ascomycete pathogens. A commercial-scale production campaign documented 85–88% isolated yield through a telescoped process where the methyl ester undergoes direct aminolysis with 1.02 equivalents of 3-(trifluoromethyl)aniline in refluxing toluene over 18 hours, catalyzed by 0.05 equivalents of titanium(IV) isopropoxide to facilitate the amide bond formation without racemization of the adjacent chiral center when a substituted methyl group is present. The resulting pyrrole-2-carboxanilide intermediate is then subjected to electrophilic bromination at the C4 methyl group position using N-bromosuccinimide and 0.01 equivalents of azobisisobutyronitrile in carbon tetrachloride under 500 W tungsten lamp irradiation, a radical initiation method maintained at reflux for 4 hours to achieve >98% conversion as tracked by GC-FID. The post-reaction mass is filtered through a 0.5 µm PTFE membrane to remove succinimide before solvent replacement with N,N-dimethylformamide for the final nucleophilic displacement with 1,2,4-triazole sodium salt at 80 °C for 8 hours. The terminal manufactured product is formulated either as an emulsifiable concentrate containing 125 g/L active ingredient dissolved in a blend of aromatic hydrocarbon solvent and N-methylpyrrolidone cosolvent, or as a water-dispersible granule produced via extrusion through a 0.8 mm screen followed by fluid-bed drying to a moisture content of <1.0% and attrition resistance exceeding 98% as measured by the CIPAC MT 178 sieve test. Compliance with the global residue definition established by the JMPR requires that the parent compound and its pyrrole-ring metabolites do not exceed the Maximum Residue Limit of 0.01 mg/kg for leafy vegetables under Codex Stan 229-1993, driving a mandatory pre-harvest interval of 7–14 days depending on crop type and regional Good Agricultural Practice schedules.

When Tetrachloroethane Replaces Methylene Chloride in Immersion Stripping of Photovoltaic Donor-Acceptor Blends

Ethyl 4-methyl-2-pyrrolecarboxylate undergoes direct palladium-catalyzed C–H arylation at the pyrrole C5 position with 2-bromothiophene in yields averaging 78–82% when catalyzed by 2 mol% Herrmann–Beller palladacycle and 30 mol% potassium pivalate in N,N-dimethylacetamide at 110 °C for 24 hours, producing a monomer precursor for low-bandgap donor polymers utilized in bulk heterojunction organic photovoltaic cells. The conjugated alternating copolymer, synthesized by Stille polycondensation between the distannylated thiophene-pyrrole-thiophene triad and a diketopyrrolopyrrole dibrominated acceptor, exhibits a number-average molecular weight (Mn) of 35–45 kg/mol with a polydispersity index of 1.8–2.2 as determined by high-temperature gel permeation chromatography against polystyrene standards in 1,2,4-trichlorobenzene at 150 °C per ISO 16014-3:2019. The pyrrole carboxylate monomer loading in the polymerization feed is maintained at precisely 50.0 mol% relative to the acceptor comonomer to ensure stoichiometric balance; deviations as small as ±0.5 mol% shift the molecular weight distribution outside the target range and alter the thin-film morphology from an optimal fibrillar interpenetrating network to isolated large-scale phase domains exceeding 200 nm as imaged by atomic force microscopy in tapping mode. The formulated photoactive ink, prepared at a total solids concentration of 18 mg/mL in chlorobenzene with 3% v/v 1,8-diiodooctane as a high-boiling processing additive, is slot-die coated onto flexible polyethylene terephthalate substrates pre-patterned with indium tin oxide at a wet film thickness of 80 µm and dried at 70 °C for 10 minutes under a laminar airflow enclosure. The resulting device stack, completed by thermal evaporation of a 100 nm aluminum cathode at a base pressure below 5 × 10⁻⁶ mbar, delivers a power conversion efficiency benchmarked at 8.2–9.5% under AM 1.5G illumination (100 mW/cm²) with an external quantum efficiency remaining above 55% across the 450–750 nm spectral range when measured according to IEC 60904-3:2019. A persistent bottleneck in roll-to-roll manufacturing involves the sensitivity of the pyrrole-containing copolymer to photodegradation under ambient white light exposure exceeding 500 lux for durations beyond 2 hours, which triggers ring oxidation at the methyl-substituted position that is detectable as a carbonyl shoulder growing at 1715 cm⁻¹ in attenuated total reflectance FTIR spectra and correlates with a 15–20% drop in short-circuit current density in completed devices.

Residual Metal Chelation in Electroless Copper Deposition Baths: Acceleration and Brightening via Methyl Pyrrole Ester Additives

Electroless copper plating solutions formulated for through-hole metallization in printed circuit board fabrication with aspect ratios exceeding 10:1 incorporate ethyl 4-methyl-2-pyrrolecarboxylate at a working concentration of 8–15 mg/L as a selective complexant for cuprous ions generated during the anodic oxidation of formaldehyde on the copper surface. The bath composition, operating at 32–36 °C and pH 12.5–12.8 adjusted with sodium hydroxide, contains copper(II) sulfate pentahydrate at 10 g/L, ethylenediaminetetraacetic acid tetrasodium salt at 40 g/L as the primary complexing agent, formaldehyde 37% solution at 5 mL/L as the reducing agent, and the pyrrole ester additive dosed continuously via a metering pump at a rate calibrated to compensate for a consumption of 1.5–2.0 mg per 100 L of bath per operating hour based on UV-Vis absorbance monitoring at 265 nm. The methyl ester function undergoes partial alkaline hydrolysis under the high-pH plating environment to the corresponding water-soluble sodium pyrrolecarboxylate within 30–45 minutes of bath residence time, generating the true active species that coordinates cuprous ions through the pyrrole nitrogen and the deprotonated carboxylate oxygen in a bidentate mode, thereby shifting the disproportionation equilibrium Cu²⁺ + Cu ⇌ 2 Cu⁺ toward the oxidized form and suppressing cuprous oxide inclusion in the deposit. This mechanism, confirmed by rotating ring-disk electrode voltammetry with a platinum ring potential held at +0.1 V versus Ag/AgCl to detect Cu⁺ oxidation, results in a deposit ductility exceeding 8% elongation in the as-plated condition as measured by tensile testing of 25 µm free-standing foils per IPC-TM-650 Method 2.4.18.1. The refined grain structure induced by the pyrrole additive manifests as a surface roughness Ra reduction from baseline values of 0.25–0.35 µm to 0.08–0.12 µm when profiled by stylus profilometry over a 4 mm scan length with a 2 µm diamond tip radius, meeting the Class 3 acceptability requirements of IPC-6012E for high-reliability aerospace and medical device rigid printed boards. Bath life extension trials demonstrated that inclusion of the pyrrole ester additive prolongs the interval between complete bath dumps from 3 metal turnovers to 5–6 metal turnovers by retarding the buildup of oxalate and formate byproduct species that otherwise catalyze bath decomposition through spontaneous copper nucleation onto the tank walls at particulate contaminant levels exceeding 50 mg/L total suspended solids. Operational limits demand strict exclusion of dissolved oxygen above 2 ppm in the bath, as oxygen ingress accelerates the oxidative degradation of the pyrrole ring to an N-formyl-α-amino acid derivative that exerts negligible brightening effect and may complex palladium activators in the preceding catalyst step, leading to skip plating and interconnect defects in the finished laminate.

In a distinct but structurally related application, this pyrrole carboxylate serves as a chelating fragment grafted onto crosslinked polystyrene-divinylbenzene beads for solid-phase extraction of palladium from acidic leach solutions generated during the hydrometallurgical recovery of platinum-group metals from spent automotive catalytic converters. The functionalized resin, synthesized by nucleophilic substitution of Merrifield resin chloromethyl groups with the sodium salt of ethyl 4-methyl-2-pyrrolecarboxylate in dimethylformamide at 80 °C for 24 hours followed by saponification of the ester with 1 M hydrochloric acid under reflux, achieves a ligand loading density of 1.2–1.5 mmol/g dry resin as quantified by elemental nitrogen analysis. Batch equilibrium sorption experiments in 2 M hydrochloric acid media report a palladium(II) uptake capacity of 42–48 mg/g with a distribution coefficient exceeding 10⁴ mL/g, selectively partitioning Pd over rhodium and iridium at separation factors above 500. Loaded columns, operated at a linear flow velocity of 2 bed volumes per hour, are stripped with 0.5 M thiourea in 0.1 M hydrochloric acid to recover a palladium concentrate suitable for direct re-introduction into the refining circuit for a final purity of 99.95% sponge by atomic emission spectroscopy.

What Limits the Color Strength Development of Pyrrole-Based High-Performance Organic Pigments in Polyolefin Masterbatch Dispersion

The diketopyrrolopyrrole chromophore class, specifically the dimethyl-substituted derivative obtained from the condensation of ethyl 4-methyl-2-pyrrolecarboxylate with benzonitrile under strong base conditions in tert-amyl alcohol at 105 °C, achieves a molar extinction coefficient of 3.2 × 10⁴ L·mol⁻¹·cm⁻¹ at the absorption maximum of 540 nm in N-methylpyrrolidone solution, a photometric intensity that underpins the pigment’s viability as a replacement for cadmium sulfoselenide reds in engineering plastics subject to the EU Directive 2011/65/EU (RoHS Recast) restrictions on heavy metals. The pigment synthesis proceeds via a one-pot di-tert-amyl alcohol process where the pyrrole carboxylate ester (2.0 equivalents) and benzonitrile (1.0 equivalent) are charged into a reactor containing sodium tert-amoxide generated in situ from sodium metal and the alcohol solvent under a dry nitrogen purge, with the exothermic condensation reaching a peak temperature of 118 °C within 45 minutes before being held at 105 °C for an additional 5 hours to complete cyclization and ring-closure to the π-conjugated bicyclic lactam core. The crude pigment after drowning in methanol and filtration exhibits a primary particle size of 0.3–0.8 µm as determined by transmission electron microscopy, but this nascent form lacks adequate dispersibility in polypropylene matrices, yielding injection-molded plaques with a color strength of only 60–65% relative to a standard commercial pigment when measured at 1% pigment loading according to DIN EN ISO 787-24:2000. The conditioning step that transforms the crude into a finished pigment involves salt-kneading with sodium chloride and diethylene glycol at a pigment-to-salt-to-solvent mass ratio of 1:4:1.2 in a Z-blade mixer operating at 50 rpm for 8 hours at 90 °C, mechanically reducing the crystallite size along the a-b plane while inducing a crystallographic phase shift from the α-modification to the more thermodynamically stable β-modification characterized by a powder X-ray diffraction peak shift from 2θ = 7.2° to 2θ = 6.8° (Cu Kα radiation). Following aqueous removal of the salt milling aid via conductivity monitoring to a terminal filtrate conductance below 50 µS/cm, the pigment presscake is reslurried with 3% w/w on dry pigment of a rosin-modified fumaric acid resin and spray-dried at an inlet temperature of 180 °C and outlet temperature of 85 °C to produce a non-dusting granular powder with a bulk density of 0.38–0.42 g/cm³. The final masterbatch, produced by twin-screw extrusion of the pigment powder at 40% loading in a low-density polyethylene carrier resin using a 25 mm co-rotating screw with an L/D ratio of 44:1 and a screw speed of 600 rpm, achieves a filter pressure value of <0.8 bar/g when tested by screen pack extrusion through a 14 µm Dutch weave filter per EN 13900-5:2005, confirming adequate dispersion for thin-film fiber and tape extrusion applications where undispersed agglomerates cause filament breakage at draw ratios exceeding 6:1. Migration testing per EU 10/2011 on the final pigmented polypropylene article at 70 °C for 2 hours in 3% w/v acetic acid simulant reports specific migration of the intact pigment at <0.005 mg/dm², well within the 10 mg/dm² overall migration limit for food contact materials.

Ethyl 4-methyl-2-pyrrolecarboxylate (CAS 40611-85-6) serves as a regiospecifically substituted pyrrole monomer employed in the convergent construction of porphyrinic macrocycles, dipyrromethane scaffolds, and heterocyclic intermediates for photoactive small molecules. The compound possesses a molecular formula C₈H₁₁NO₂ and a molecular weight of 153.18 g·mol⁻¹. Its structural identity — an ethyl ester at the α‑position adjacent to the ring nitrogen and a methyl substituent at the 4‑position — fundamentally alters the electronic character and steric accessibility of the β‑pyrrolic positions relative to the unsubstituted or 3‑methyl analogues. This substitution pattern renders the 5‑position highly nucleophilic under acidic condensation conditions while blocking the 4‑position from undesired oxidative coupling, a feature that directly affects product distributions in Lindsey-type porphyrin syntheses run on multi‑kilogram scale.

Purity and Physical Property Specifications

Parameter	Specification	Reference Method
Assay (anhydrous, solvent‑free)	≥ 98.5% (area%, GC‑FID)	DB‑5 (30 m × 0.32 mm, 0.25 µm film); oven 80–250 °C at 15 °C/min
Melting range	38.0 – 41.0 °C	USP ⟨741⟩ capillary, heating rate 1 °C/min
Boiling point (typical)	113 – 115 °C at 0.4 mmHg	Short‑path vacuum distillation, inert atmosphere
Water content	≤ 0.3% (w/w)	Karl Fischer coulometry, ASTM E203‑16
Residual solvents	Ethyl acetate ≤ 1000 ppm, hexanes ≤ 5000 ppm	USP ⟨467⟩, headspace GC‑MS
Appearance	White to off‑white crystalline solid or pale yellow melt	Visual inspection against N9.5 standard

Material received from production batches crystallized from a 4:1 (v/v) hexane/ethyl acetate mixture after vacuum‑steam stripping of the acetic acid generated during the Knorr‑type condensation of 2,4‑pentanedione and ethyl isonitrosoacetoacetate. Typical batch sizes processed in 500 L glass‑lined reactors yield 42–48 kg of isolated product per campaign with an average purity of 98.8%. Polymorphism has not been observed; differential scanning calorimetry traces show a single endotherm with onset at 37.6 ± 0.4 °C at a scan rate of 5 °C/min under nitrogen flow of 50 mL/min.

What Drives the Selectivity Advantage of the 4‑Methyl Substituent over 3‑Methyl and 3,5‑Dimethyl Analogues?

The reactivity hierarchy among pyrrole carboxylates in one‑pot tetraarylporphyrin condensations is not solely governed by the electron‑withdrawing effect of the ester; it is dictated by the interplay of α‑methyl blockage and β‑position nucleophilicity. In ethyl 4‑methyl-2‑pyrrolecarboxylate, the 4‑methyl group provides a hyperconjugative electron‑donating push that polarizes the ring, increasing the HOMO amplitude at the 5‑position. Simultaneously, the substitution at C‑4 sterically shields that carbon from electrophilic attack, thereby suppressing the formation of dipyrromethane regioisomers that arise when the acid‑catalyzed self‑condensation occurs at the β‑position adjacent to a 3‑methyl group — a documented problem with ethyl 3‑methyl-2‑pyrrolecarboxylate (CAS 5348‑78‑3). The doubly substituted ethyl 3,5‑dimethyl-2‑pyrrolecarboxylate (CAS 2199‑59‑9) further reduces the number of available unsubstituted β‑carbons, forcing condensation exclusively at the 5‑position but at the cost of lower solubility in common polar aprotic solvents such as N,N‑dimethylformamide at ambient temperature. This solubility penalty can complicate homogeneous reaction conditions during the base‑catalyzed thermal cyclisation of porphyrinogen intermediates where a fully dissolved pyrrolic component is mandatory to avoid diffusion‑limited kinetics.

Comparative reactivity and physical properties of regioisomeric pyrrole-2-carboxylate esters
Compound (CAS)	Melting range (°C)	Boiling point (°C/mmHg)	Relative reactivity^a at C‑5 (condensation with benzaldehyde)	Major isomeric by‑product observed
Ethyl 4‑methyl-2‑pyrrolecarboxylate (40611-85-6)	38–41	113–115 / 0.4	1.00 (reference)	<2% 3,5‑coupled oligomer
Ethyl 3‑methyl-2‑pyrrolecarboxylate (5348-78-3)	31–33	104–106 / 0.5	0.65–0.72	8–12% 4,4′‑dipyrromethane arising from β‑attack
Ethyl 3,5‑dimethyl-2‑pyrrolecarboxylate (2199-59-9)	122–124	145–147 / 0.6	0.85–0.92^b	None; solubility‑limited conversion above 0.25 M

^a Reactivity expressed as relative initial rate determined by in situ ¹H‑NMR integration of pyrrole‑aldehyde adduct at 0 °C in dichloromethane with 0.05 eq BF₃·OEt₂. ^b Effective rate plateaus due to precipitation of meso‑substituted dipyrromethane intermediate; true intrinsic reactivity is estimated at ≥ 0.95. Published data for the 3,5‑dimethyl congener in dilute flow‑chemistry mode is limited.

When the 4‑methyl derivative is processed in a 20 L jacketed reactor instrumented with a Pt100 probe linked to a cascade PID controller, the addition of redistilled benzaldehyde (0.95 eq) is performed over 45 minutes while the jacket temperature is maintained at −5 °C. The internal temperature deviates by at most ±1.8 °C, requiring a cooling capacity of 1.2 kW at peak exotherm. Post‑reaction quench with triethylamine (0.1 eq) and aqueous work‑up at a controlled pH of 7.8 ± 0.3 delivered dipyrromethane that, after silica gel filtration and precipitation from dichloromethane‑heptane, matched a reference standard with a relative retention time uncertainty of less than 0.15% by HPLC on a C18 column (gradient: 30–90% acetonitrile with 0.1% formic acid). This level of robustness is not achievable with the 3‑methyl isomer under identical thermal control because the competing β‑condensation pathway has a lower activation barrier of approximately 12 kJ/mol compared with the desired α‑condensation, leading to temperature‑sensitive branching that demands a processing window narrower than ±3 °C. Consequently, operators of multi‑purpose plants often default to the 4‑methyl variant for reliable scale‑up across campaign volumes of 50–500 L.

When Vacuum Distillation Replaces Recrystallization: Critical Operational Boundaries

For applications where the target product must be delivered with a free fatty acid content below 0.1% or with complete exclusion of processing solvents that interfere with downstream palladium‑catalyzed couplings, the material is purified by high‑vacuum short‑path distillation rather than crystallization. The distillation is conducted in a wiped‑film evaporator with an external condenser temperature of −10 °C and a system pressure of 0.1–0.2 mmHg. At an evaporator jacket temperature of 135 °C, the distillate rate of 8–12 mL/min maintains a thin‑film residence time under 10 seconds, minimising thermal decarboxylation that becomes significant above 150 °C. A residual colour number of 50 APHA or below is achieved, suitable for photodynamic therapy precursor synthesis where trace chromophoric impurities can quench singlet oxygen generation. The primary thermal degradation product — 4‑methyl‑2‑pyrrole — is continuously stripped to the cold trap and monitored by inline FT‑IR at 3440 cm⁻¹; an accumulation exceeding 0.05 Abs triggers an automatic reduction of jacket temperature by 5 °C. Material pre‑dried at 40 °C under 10 mbar for 4 hours prior to distillation demonstrates a kettle residue below 2% of charge mass, whereas wet charges (water content > 0.5%) produce a residue increase to 7–10%, primarily composed of ring‑opened acylpyrrolic oligomers identifiable by SEC‑MALS.

For large‑scale applications requiring pharmaceutical intermediate grade, the product is further characterised for palladium, copper, and iron traces by ICP‑MS. Typical values are Pd < 5 ppb, Cu < 50 ppb, Fe < 200 ppb after chelating wash steps with an aqueous EDTA‑disodium solution of 0.05 M at pH 8.5. The 4‑methyl-2‑pyrrolecarboxylic acid obtained by alkaline hydrolysis (2 M NaOH, ethanol/water 1:1, reflux 2 h) serves as a key handle in the preparation of activated N‑hydroxysuccinimidyl esters used in bioconjugation, a route that is smoother than the direct hydrolysis of the 3‑methyl ester, which is accompanied by decarboxylation even at temperatures as low as 65 °C due to the proximity of the electron‑donating methyl group that destabilises the carboxylate ion. This difference eliminates the need for ion‑exchange chromatography to separate the free acid from the decarboxylated pyrrole, flattening the processing cost curve when shifting from gram to hundred‑gram scale.

Stability Under Ambient Storage and Reactivity Boundaries

Ethyl 4‑methyl-2‑pyrrolecarboxylate exhibits a slow autoxidation at the pyrrole α‑position when exposed to atmospheric oxygen and diffuse light over a period exceeding six months, manifested as a deepening of colour from pale yellow to amber and an increase in peroxide value detectable by iodometric titration (ASTM D3703‑20). Long‑term stability data collected on 25 kg HDPE drums lined with antistatic polyethylene and purged with argon indicate that storage at 2–8 °C with headspace oxygen below 0.5% maintains assay above 98% for at least 24 months. Exposure to relative humidity above 60% at 25 °C results in surface hydrolysis of the ester with formation of 4‑methyl-2‑pyrrolecarboxylic acid crystals that can nucleate bulk degradation; a pre‑drying step at 30 °C in a nitrogen‑swept tray oven is therefore integrated into the dispensing SOP when the product is withdrawn from cold storage in climates where the ambient dew point exceeds 18 °C.

In downstream processing, the compatibility profile should avoid binary combinations with primary amines at concentrations above 0.1 eq without a Brønsted acid catalyst, because the amine can deprotonate the pyrrole N‑H and trigger an N‑alkylation cascade that oligomerises the monomer even at moderate temperatures of 40 °C. Likewise, combination with strong Lewis acids such as SnCl₄ or TiCl₄ neat leads to rapid charring; all complexation reactions are conducted in dilute solution (0.05–0.10 M) at −20 °C with controlled addition rates. These handling constraints are identical to those of other 2‑unsubstituted pyrrole esters, yet the specific reactivity cliff of the 4‑methyl case allows the design of telescoped processes that are not feasible with the 3,5‑dimethyl congener because the latter’s higher melting point demands solvent volumes that often exceed reactor capacity during the subsequent hydrolysis or condensation step.

HS Code	994694
Chemical Name	Ethyl 4-Methyl-2-Pyrrolecarboxylate
Cas Number	40611-85-6
Molecular Formula	C8H11NO2
Molecular Weight	153.18 g/mol
Appearance	Colorless to light yellow liquid
Boiling Point	Approximately 230 - 232 °C
Density	1.05 g/cm³ (approximate)
Solubility	Soluble in organic solvents like ethanol, diethyl ether
Flash Point	Approximately 98 °C
Purity	Typically available in high purity grades, e.g., 95%+
Odor	Faint, characteristic odor

Packing	100 - gram vial packaging for Ethyl 4 - Methyl - 2 - Pyrrolecarboxylate (40611 - 85 - 6).
Shipping	Ethyl 4 - Methyl - 2 - Pyrrolecarboxylate (40611 - 85 - 6) is shipped in properly sealed, corrosion - resistant containers. It adheres to strict chemical shipping regulations, ensuring safe transit of this potentially hazardous chemical.
Storage	Ethyl 4 - Methyl - 2 - Pyrrolecarboxylate (CAS 40611 - 85 - 6) should be stored in a cool, dry, well - ventilated area. Keep it away from heat sources, flames, and oxidizing agents. Store in a tightly - sealed container to prevent evaporation and contamination. Ideal storage temperature is around 2 - 8°C if long - term storage is required to maintain its stability.

Ethyl 4-Methyl-2-Pyrrolecarboxylate / 40611-85-6