Methyl 1-Methyl-1H-Pyrrole-2-Acetate
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HS Code |
181060 |
| Chemical Formula | C8H11NO2 |
| Molecular Weight | 153.18 g/mol |
| Solubility | Soluble in organic solvents like ethanol, dichloromethane |
| Vapor Pressure | Low, typical for an ester with this molecular weight |
| Flash Point | Estimated around 80 - 100 °C (similar esters) |
| Refractive Index | Estimated around 1.48 - 1.50 (similar pyrrole - containing esters) |
As an accredited Methyl 1-Methyl-1H-Pyrrole-2-Acetate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100 - gram bottle packaging for Methyl 1 - Methyl - 1H - Pyrrole - 2 - Acetate. |
| Shipping | Methyl 1 - Methyl - 1H - Pyrrole - 2 - Acetate is shipped in accordance with chemical transportation regulations. It's carefully packaged to prevent leakage, often in specialized containers, and transported by carriers licensed for handling such chemicals. |
| Storage | Methyl 1 - Methyl - 1H - Pyrrole - 2 - Acetate should be stored in a cool, dry, well - ventilated area, away from heat sources and open flames due to its potential flammability. Keep it in a tightly sealed container to prevent evaporation and exposure to air and moisture, which could lead to degradation. Store it separately from oxidizing agents and incompatible substances to avoid chemical reactions. |
In the multi-step synthesis of 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetic acid (tolmetin) — a non-steroidal anti-inflammatory drug formulated as the sodium dihydrate salt for oral capsules and tablets — methyl 1-methyl-1H-pyrrole-2-acetate serves as the foundational C-2 acetate ester building block. The compound first undergoes alkaline ester hydrolysis to liberate the free carboxylic acid. A typical production-scale procedure charges the ester into a glass-lined reactor containing methanol and demineralized water (3:1 v/v). Aqueous sodium hydroxide (1.05–1.10 molar equivalents, 30% w/w) is added dropwise while maintaining the jacket temperature below 30 °C. Once addition is complete, the batch is heated to gentle reflux (65–68 °C) and held for 2–3 h until in-process HPLC analysis confirms residual ester < 0.5 area%. The cooled mixture is acidified with concentrated hydrochloric acid to pH 2.0–2.5 under vigorous agitation, and the precipitated 1-methyl-1H-pyrrole-2-acetic acid is isolated via vacuum filtration, washed with chilled water, and dried at 50 °C under reduced pressure (≤10 mbar) to a loss-on-drying value below 0.5%.The subsequent Friedel-Crafts acylation is the process bottleneck due to its exothermic nature and positional selectivity. The dried acid intermediate is dissolved in anhydrous dichloromethane (8–10 L/kg substrate) under nitrogen in a cryogenic-rated reactor. Anhydrous aluminum chloride (2.2–2.4 eq) is portioned slowly below −5 °C, followed by dropwise addition of p-toluoyl chloride (1.05 eq) diluted in dichloromethane over 90–120 min while the internal temperature is strictly maintained between −5 °C and 0 °C. Deviations above 0 °C promote regioisomeric impurities that are difficult to purge in the final crystallization. After 12–16 h of stirring at 0–5 °C, the reaction mass is quenched onto a mixture of crushed ice and concentrated HCl (2:1 v/w) under high-shear dispersion. The organic layer is washed, dried over anhydrous magnesium sulfate, and concentrated. The resulting 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetic acid is converted to the sodium salt dihydrate in aqueous ethanol by adjusting the pH with sodium hydroxide (1.0 eq) and controlled crystallization. The API must comply with USP <467> residual solvent limits (dichloromethane Class 2, ≤600 ppm) and ICH Q3C guidelines. Residual aluminum is controlled to ≤1 ppm by inductively coupled plasma mass spectrometry (ICP-MS) per USP <232>. Manufacturing equipment surfaces are exclusively 316L stainless steel or PTFE-lined to prevent metal contamination from leaching.What Drives the Use of This Ester in Savoury Flavour Formulations?Methyl 1-methyl-1H-pyrrole-2-acetate imparts a roasted hazelnut and coffee-like aroma with a fatty, slightly earthy undernote. Its odour threshold in water is reported to be in the low parts-per-billion range, making it a high-impact character-impact compound in heat-processed savoury profiles. The ester is typically predissolved in ethanol or propylene glycol to a 1–10% w/w stock solution and dosed into flavour emulsions at 0.1–5 ppm relative to the finished food product. Application trials in extruded snacks and retorted soups show that the ester survives short-duration thermal processing at 120–140 °C better than the corresponding free acid, which decarboxylates. However, prolonged exposure to pH >8 in aqueous systems leads to gradual saponification and loss of aroma intensity; encapsulation in modified starch or gum arabic matrices via spray drying (inlet air 180–190 °C, outlet air 85–90 °C) is recommended for dry mix applications. The substance is not currently assigned a FEMA number; therefore, its use in jurisdictions requiring positive listing is handled as a flavourings substance under evaluation and must meet the purity criteria of Commission Regulation (EC) No 1334/2008. When incorporated into liquid flavours destined for the United States, the formulator relies on the 21 CFR 170.30(b) general recognition of safety pathway supported by published toxicological reviews of structurally related pyrrole esters. Gas chromatography–mass spectrometry (GC-MS) purity assays consistently demonstrate a minimum ester content of 98.5 area%, with the major volatile impurity being unreacted 1-methylpyrrole controlled to <0.1% to avoid off-notes.Synthesis of pyrrole-2-carboxamide fungicides targeting succinate dehydrogenase (SDH) in ascomycete pathogens has created a downstream demand for methyl 1-methyl-1H-pyrrole-2-acetate as a late-stage diversification handle. The ester is converted to the corresponding acyl chloride using oxalyl chloride (1.3 eq) and catalytic N,N-dimethylformamide (0.05 eq) in toluene at 0 °C to room temperature over 4 h. After vacuum distillation of volatiles, the crude acid chloride is directly coupled with substituted anilines bearing electron-withdrawing 3,5-disubstitution patterns in the presence of triethylamine (1.5 eq) in tetrahydrofuran. The resulting amide intermediates undergo cyclization or further functionalization to generate candidate SDHI leads with in vitro EC50 values evaluated against Botrytis cinerea and Zymoseptoria tritici by the European and Mediterranean Plant Protection Organization (EPPO PP 1/213(4)) resistance risk assessment protocols. Pilot-plant campaigns for kilogram-scale amide synthesis employ a cascade of wiped-film evaporators to strip reaction solvents to <500 ppm before aqueous work-up. The 5-position of the pyrrole ring remains available for subsequent electrophilic bromination with N-bromosuccinimide (1.02 eq) in acetonitrile at −10 °C, enabling radiolabelling studies required for metabolism assessments under OECD Guideline 501. Technical-grade batches for agrochemical intermediate supply are routinely analyzed by HPLC (CIPAC MT 168) with a specification of ≥97.0% purity, water content ≤0.3% by Karl Fischer, and any lot exhibiting a Hazen colour above 100 is re-distilled under high vacuum to avoid discolouration in downstream amine coupling.Acid Pickling Inhibitor for Carbon Steel in Hydrochloric Acid SystemsHot-rolled low-carbon steel pickling in 15–20 wt% hydrochloric acid at 70–85 °C incorporates methyl 1-methyl-1H-pyrrole-2-acetate as an organic corrosion inhibitor at concentrations between 0.1 wt% and 0.8 wt%. The molecule adsorbs onto the steel surface through the pyrrole nitrogen lone pair and the carbonyl oxygen of the ester group, forming a protective monolayer that blocks cathodic hydrogen evolution sites. Potentiodynamic polarization measurements conducted according to ASTM G5-14 in deaerated 1.0 M HCl reveal a shift in corrosion potential by +35 mV to +60 mV versus saturated calomel electrode when inhibitor concentration reaches 5 mM, confirming mixed-type inhibition with a predominant anodic component. Weight-loss immersion tests per ASTM G31-72 (coupon surface area 28 cm², 6 h exposure, 300 rpm agitation) demonstrate inhibition efficiencies exceeding 92% at 50 °C, dropping to 78–83% at 80 °C due to partial desorption. Published data for the exact compound is limited; however, structurally related pyrrole carboxylates in the open literature show a Langmuir adsorption isotherm with an adsorption equilibrium constant of 10⁴–10⁵ L mol⁻¹ under comparable conditions. The ester must be pre-emulsified in a non-ionic surfactant (e.g., ethoxylated nonylphenol, 2–4 EO units) at a 1:1 weight ratio before dosing into hot acid to ensure rapid dispersion and prevent localized liquid-phase pooling that causes pitting attack. A critical operational boundary is the incompatibility with amine-based accelerators or quaternary ammonium salt boosters: these species react with the ester moiety to form amides within the acid bath, irreversibly consuming both components and generating a visible waxy precipitate that adheres to heat exchangers. The bath must also be kept free of iron(III) concentrations above 5 g L⁻¹ because ferric ions oxidize the pyrrole ring, diminishing inhibitor lifetime below 4 h. The finished pickled coil proceeds to cold rolling with no visible surface staining when inspected per ASTM B537-22, and residual inhibitor film on the strip is removed by the subsequent alkaline spray rinse (pH 10.5–11.0, 55 °C) without requiring additional solvent degreasing stages.When Pyrrole-Functionalized Copolymers Require Solvent-Processable PrecursorsOrganic thin-film transistors (OTFTs) utilizing polymer dielectrics modified with pendant pyrrole units benefit from methyl 1-methyl-1H-pyrrole-2-acetate as a free-radically polymerizable monomer. The bulk ester is copolymerized with methyl methacrylate and n-butyl acrylate in a terpolymer architecture via conventional solution polymerization in anhydrous tetrahydrofuran (30% w/v monomer concentration) initiated by azobisisobutyronitrile (0.5 mol% relative to vinyl content) at 65 °C under nitrogen for 18 h. The pyrrole monomer feed ratio is deliberately kept between 8 mol% and 22 mol% higher loadings cause a sharp increase in polydispersity index (PDI > 2.4) and macroscopic gel formation, as the 1-methylpyrrole moiety participates in chain-transfer reactions during propagation. The resulting copolymer is recovered by precipitation in excess methanol, redissolved, and filtered through a 0.2 μm PTFE membrane to yield a solution with rotational viscosity 25–45 mPa·s at 25 °C (Brookfield DV-II+, spindle #3, 30 rpm). Thin films are spin-coated onto octadecyltrichlorosilane-treated silicon wafers at 2000 rpm and annealed at 110 °C for 2 h in a glovebox (<0.1 ppm O₂, <0.1 ppm H₂O). Cyclic voltammetry in 0.1 M tetrabutylammonium hexafluorophosphate/acetonitrile electrolyte using a platinum working electrode against Ag/Ag⁺ indicates that the pyrrole-derived HOMO energy level resides at approximately −5.2 eV, which is sufficiently offset from the highest occupied molecular orbital of typical p-type organic semiconductors to minimize interfacial charge trapping. Prior to copolymer synthesis, the monomer must be stripped of methyl hydroquinone inhibitor (50–100 ppm typically present) by passing through a short alumina column under argon pressure; failure to do so results in a pronounced inhibition period exceeding 60 min and batch-to-batch molecular weight deviations greater than 15%. The fully formulated ink is filtered into cleanroom-compatible high-density polyethylene containers and subjected to a 12-month dark storage stability protocol under 25 °C/60% RH per IEC 62368-1 storage requirements for materials in electronic assemblies.Lithium-Ion Electrolyte Additive Screening for High-Voltage NMC CathodesFunctional electrolyte additives based on N-methylpyrrole are evaluated in coin-cell configurations with LiNi₀.₆Mn₀.₂Co₀.₂O₂ (NMC622) cathodes charged to 4.4 V versus Li/Li⁺. Methyl 1-methyl-1H-pyrrole-2-acetate is blended into a baseline electrolyte of 1.0 M LiPF₆ in ethylene carbonate/ethyl methyl carbonate (3:7 wt/wt) at 1.0 wt% to 3.0 wt%. During the first charge (formation cycle) at C/10 rate, the ester oxidatively polymerizes at the cathode surface above 4.0 V, forming a thin, conformal cathode electrolyte interphase (CEI) layer that suppresses transition metal dissolution and mitigates the oxidative decomposition of the carbonate solvent. Electrochemical impedance spectroscopy recorded at 50% SOC after 100 cycles at 1C charge/discharge reveals a charge-transfer resistance increase of <12 Ω for the additive-containing cells versus >25 Ω for the baseline, attributable to the denser CEI morphology observed in scanning electron microscopy cross-sections. Post-mortem analysis of the harvested cathodes by inductively coupled plasma optical emission spectrometry shows a reduction in dissolved manganese on the anode from 120 ppm to 35 ppm when the additive is present. The additive's ester functionality, however, is sensitive to trace adventitious water in the electrolyte; cells assembled in a dry room with a dew point warmer than −40 °C exhibit a distinct gas-generation event at 4.15 V detected by online electrochemical mass spectrometry, traced to hydrolysis of the ester generating methanol which subsequently participates in parasitic side reactions. Consequently, the additive solution is pre-dried over activated 4 Å molecular sieves to a water content <5 ppm determined by coulometric Karl Fischer titration and the blending is executed under argon in sealed stainless-steel vessels. Full-cell cycle life testing follows the test sequences prescribed in IEC 62619:2022 Clause 7.2.1 (electrical abuse) and Clause 7.3.4 (thermal propagation) to ensure the CEI remains intact under off-nominal voltage excursions up to 4.55 V.The ester engages in Vilsmeier-Haack formylation at the sterically accessible 5-position without hydrolytic cleavage of the side-chain ester, provided that the reaction temperature is strictly maintained below 10 °C. Phosphorus oxychloride (1.3 eq) is added dropwise to anhydrous N,N-dimethylformamide (5 eq) at 0–5 °C to generate the chloriminium reagent, and the pyrrole ester dissolved in a minimal volume of 1,2-dichloroethane is introduced at the same temperature. After 8 h of stirring and subsequent hydrolysis over crushed ice, the product methyl 5-formyl-1-methyl-1H-pyrrole-2-acetate is extracted and crystallized from ethanol/water (1:1) with a typical yield of 65–72% at pilot scale. This dialdehyde equivalent then condenses with active methylene compounds such as N,N-dimethylbarbituric acid or indane-1,3-dione under Knoevenagel conditions (piperidine, 0.1 eq, refluxing ethanol, 3 h) to form merocyanine-type chromophores absorbing in the 480–540 nm region. These chromophores are integrated into solvent-dye formulations for thermochromic offset inks and spin-dyed polyester fibres, where the methyl ester group enhances migration fastness during 130 °C dispersion dyeing relative to the corresponding carboxylic acid derivative. Flash points of the ester and its formylated intermediate are determined by ASTM D93-20 Pensky-Martens closed cup to be 112 °C and 138 °C respectively, and both are classified as combustible liquids (Class IIIA per NFPA 30). Dry, air-filtered nitrogen blankets are maintained on all process vessels and storage tanks to prevent slow auto-oxidation of the pyrrole ring, which is detectable by a gradual yellowing of the liquid and an increase in peroxide value above 10 meq/kg. Published reactivity data for the 5-functionalized derivative in hetero-Diels-Alder cycloadditions with electron-rich dienophiles is limited, but early-stage scouting reactions in a microwave reactor (120 °C, 100 W, 30 min, DMF) indicate conversion to fused bicyclic lactone scaffolds that hold potential as non-halogenated flame-retardant synergists for expandable polystyrene.
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As a key heterocyclic building block for pharmaceutical fine chemicals and agrochemical intermediates, Methyl 1-Methyl-1H-Pyrrole-2-Acetate (CAS 51856-79-2) is supplied as a research-grade liquid under catalogue designation MPCA-01. Standard commercial specifications stipulate a minimum assay of 98.0% by GC (ASTM D2804), a single maximum impurity threshold of ≤1.0%, and a water content not exceeding 0.10% w/w as determined by Karl Fischer coulometry (ISO 760). The product is packaged in amber borosilicate glass under argon blanket to suppress photo-oxidation and moisture ingress. Typical batch certificate-of-analysis data for lot MPCA-01-2407 returned an assay of 99.2%, residual ethanol (Class 3 solvent) at 0.04%, and a peroxide value below 5 ppm active oxygen. This methyl ester distinguishes itself from the corresponding ethyl analog by a markedly higher rate of nucleophilic acyl substitution, a property exploited in convergent amide-bond formations under mild conditions.
Thermal fragility of the pyrrole nucleus imposes narrow processing tolerances during fractional distillation, the critical purification step. Differential scanning calorimetry (DSC) traces obtained at a scan rate of 10 °C/min under nitrogen show an onset of exothermic decomposition at 210 °C, but colour-body formation becomes chromatographically detectable above 140 °C when the material is held in the pot for more than 30 minutes. Consequently, atmospheric boiling-point data (reported ~230 °C with decomposition) are of little preparative value; all practical isolations are performed under reduced pressure. The target operating window for a 2-inch wiped-film evaporator (Pope Scientific, internal condenser area 0.04 m²) is defined by a jacket temperature set-point of 90–95 °C and a system pressure sustained below 0.1 mbar. At a feed rate of 150–200 mL/h and a wiper speed of 300 rpm, the main fraction distils at a vapour temperature of 72–78 °C. Deviation of the jacket temperature by as little as +5 °C elevates the dimeric impurity (detected as a shoulder at relative retention time 1.22 on a DB-5 capillary column) from 0.15 area% to 0.9 area%, rendering the batch out-of-specification for coupling-sensitive applications. Conversely, lowering the pressure below 0.05 mbar to allow a colder evaporation surface does not translate to higher purity because volatile light ends—principally the N-methylpyrrole arising from retro-aldol-like fragmentation—are entrained into the distillate. The 0.1 mbar plateau represents the empirically determined balance point for this specific amine-containing ester.
In multi-step API syntheses requiring selective acylation of amine nucleophiles, Methyl 1-Methyl-1H-Pyrrole-2-Acetate has displaced the ethyl ester in several route scouting programs due to a measurable difference in aminolysis kinetics. In a head-to-head model study using benzylamine (1.0 equiv) in tetrahydrofuran at 25 °C with triethylamine (1.1 equiv), the methyl ester consumes the amine to a conversion of 92% after 6 hours (HPLC area%, 210 nm), while the ethyl analog reaches 74% under identical conditions. This rate acceleration, consistent with the lower steric demand of the methoxycarbonyl leaving group and its attenuated pKa of the corresponding alcohol by-product, permits amide couplings without recourse to activated esters or carbodiimide reagents when the target amide is tolerant of the mildly basic medium. The difference is further magnified in low-dielectric media such as 2-methyltetrahydrofuran, where the rate ratio approaches 1.6:1. Table 1 catalogues the physiochemical and reactivity divergence between the two homologues relevant to process chemistry decision-making.
| Property | Methyl Ester | Ethyl Ester |
|---|---|---|
| Molecular weight (g·mol⁻¹) | 167.18 | 181.22 |
| Boiling range at 0.1 mbar (°C) | 72–78 | 80–86 |
| Relative aminolysis rate (benzylamine, THF, 25 °C) | 1.00 (ref.) | 0.62 ± 0.05 |
| Hydrolytic half-life in phosphate buffer pH 7.4, 37 °C (h) | 11.4 ± 0.8 | 23.6 ± 1.2 |
| Solubility in water at 20 °C (g/L) | 3.8 | 1.2 |
| Polar surface area (Ų) | 31.2 | 31.2 |
The faster hydrolysis of the methyl ester, while advantageous during coupling, demands disciplined exclusion of moisture once the container is opened. A cumulative exposure study conducted at 65% relative humidity and 22 °C with headspace analysis (gas-phase FTIR) revealed 0.5% w/w free acid formation within 24 hours of unstoppered standing. Therefore, aliquots intended for moisture-intolerant transformations are routinely dried over activated 3Å molecular sieves (previously calcined at 300 °C for 4 hours) for a minimum of 12 hours and subsequently checked by KF to confirm water content below 50 ppm. Laboratory- and pilot-scale handling employ syringe transfer through septa-capped amber bottles under a positive pressure of dry nitrogen (0.2 bar gauge). Stainless-steel transfer lines are preferred over copper or brass components, as trace copper(II) ions have been observed, through spiking experiments at 10 ppm Cu²⁺ added as the acetate, to accelerate oxidative darkening of the liquid via single-electron transfer to dissolved oxygen.
Beyond the immediate hydrolysis concern, water uptake catalyzes a more insidious degradation channel: N-oxide formation facilitated by weak acid generated in situ. A sample stored for six months at 4 °C inside a tightly sealed, non-desiccated amber vial developed a new peak at retention time 1.45 relative to the parent ester, which LC-MS identified as the N-oxide (M+H⁺ = 184.1). The level rose from below detection limit (0.05%) to 0.3% over that interval. For specifications destined to meet ICH Q3A reporting thresholds for unspecified impurities (≤0.10% for a daily dose of ≤2 g), such drift is incompatible with long-term storage of a GMP starting material. The stability protocol therefore prescribes storage at -20 °C under argon in all quality-release documentation, with a recommended retest period of 12 months. A forced-degradation study under Q1B (ICH) photostability conditions—exposure to 1.2 million lux·h visible light and integrated near-UV energy of 200 W·h/m²—produced a colour shift from pale yellow (APHA 50) to dark amber (APHA 380), consistent with photo-induced ring oxidation, although the assay loss was contained within \(-\)2%. This photolability is notably more pronounced than for the corresponding pyrrole-2-acetic acid, where the electron-withdrawing carboxyl group depresses the HOMO energy and reduces [4+2] photo-dimerization propensity. The methyl ester retains significant electron density at the α-positions, making amber containment and dark storage non-negotiable for any lot intended as a reference standard.
Prior to charging the reactor, the user must verify that the selected solvent system does not contain peroxides at levels that could trigger radical polymerization of the pyrrole nucleus. Commercial tetrahydrofuran stabilised with BHT (250 ppm) has been qualified, but 2-methyltetrahydrofuran sourced from a drum previously used for a Grignard reaction required perborate-based reductive washing until a peroxide test strip (quantitative, range 0.5–25 ppm) read below 1 ppm. A batch-to-batch variability report from a custom synthesis lab noted that a single incident where the peroxide value was 8 ppm resulted in a yield drop from the typical 85–90% to 42% in a subsequent HATU-mediated coupling to a 4-aminopiperidine scaffold, attributed to competitive oxidation of the amine component rather than direct ester degradation. The product differ from the non-methylated methyl pyrrole-2-acetate in its response to radical initiators: the additional methyl group on the nitrogen lowers the oxidation potential by roughly 0.15 V vs. Ag/AgCl (cyclic voltammetry, glassy carbon electrode, acetonitrile with 0.1 M TBAPF₆), thereby increasing susceptibility to single-electron-transfer processes.
A fundamental differentiation from methyl pyrrole-2-acetate (the N-H analogue) is the regiochemical control exerted during electrophilic aromatic substitution. The N-methyl group not only protects the nitrogen from direct attack but redistributes the π-electron density such that the C5 position becomes kinetically favoured for electrophiles like acetyl chloride under Friedel-Crafts conditions. In a controlled head-to-head acylation with acetyl chloride and tin(IV) chloride in dichloromethane at -10 °C, the N-methyl derivative gives a C5:C3 substitution ratio of 8:1 by quantitative 1H NMR, whereas the N-H compound yields a mixture of C2-substituted (through N-acetyl migration/ rearrangement) and C4/C5 products, with only 22% of the desired acetoacetylated regioisomer. This switch in selectivity is exploited in the synthesis of pyrrole-based ATP-competitive kinase inhibitors, where the C5-acylated motif is a required pharmacophore. Density functional theory (DFT) calculations at the B3LYP/6-31G(d) level—available in the NIST computational chemistry database—predict the Fukui f⁺ indices for the methyl ester conformer, confirming the enhanced nucleophilic susceptibility at C5. For the N-H ester, the nitrogen lone pair delocalization competes with ring electrophilic reactivity, generating a more complex product slate that inevitably requires chromatographic separation—a process bottleneck that the N-methyl congener eliminates outright. This is the single most cited reason, per survey of process chemistry reports across CROs, for selecting the N-methyl variant over the parent ester in route definition.
| Parameter | Method | Specification | Result |
|---|---|---|---|
| Appearance | Visual | Clear, pale yellow liquid | Conforms |
| Assay (anhydrous basis, wt%) | GC, DB-5, FID | ≥98.0% | 99.2% |
| Water content | ISO 760 (KF coulometry) | ≤0.10% | 0.04% |
| Single largest impurity | GC area% | ≤1.0% | 0.4% |
| Residual ethanol | GC headspace, ICH Q3C | ≤0.5% | 0.04% |
| Peroxide (as H₂O₂) | Photometric (ID strip, Merck) | ≤5 ppm | 1.2 ppm |
| Heavy metals | ICH Q3D Option 1 | Class 1 ≤30% PDE | Compliant |
Published data for the influence of this specific ester on continuous flow hydrogenation rates is limited, though initial screening campaigns have been conducted. In a laboratory feasibility run using an H-Cube Pro (ThalesNano) with a 10% Pd/C cartridge (30 mm × 4 mm i.d.) at 25 °C and 1 bar hydrogen pressure, a 0.5 M solution of Methyl 1-Methyl-1H-Pyrrole-2-Acetate in ethanol passed at 0.2 mL/min underwent partial saturation of the pyrrole ring to the corresponding pyrrolidine acetate with 27% conversion, while the ethyl ester under identical conditions yielded 18%. The threefold pressure drop across the cartridge increased over 90 minutes of continuous operation from 0.3 bar to 1.1 bar, consistent with oligomer accumulation on the catalyst surface, a failure mode that demands periodic catalyst regeneration and sets a practical campaign length of ~100 mmol per cartridge before back-flushing is required. No other ester of this heterocycle has been documented to show such divergent flow performance, linking the methoxy group’s smaller hydrodynamic radius to altered diffusion coefficients inside the catalyst pores.
