4-Butanoic Acid-3-Ethyl Formate Pyrrole
|
HS Code |
379066 |
| Chemical Formula | C9H13NO3 |
| Molecular Weight | 183.205 g/mol |
| Physical State | Solid (predicted) |
| Boiling Point | Estimated around 314.5°C at 760 mmHg |
| Melting Point | No data found (common experimental techniques required for determination) |
| Density | No experimental data, predicted values may vary |
| Solubility | Soluble in organic solvents like ethanol, less soluble in water |
| Odor | No data, but may have a characteristic organic odor |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
| Flash Point | Estimated around 144.0°C |
As an accredited 4-Butanoic Acid-3-Ethyl Formate Pyrrole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 4 - Butanoic Acid - 3 - Ethyl Formate Pyrrole packaged in a sealed glass bottle. |
| Shipping | 4 - Butanoic Acid - 3 - Ethyl Formate Pyrrole is shipped in accordance with strict chemical regulations. It's packaged securely in suitable containers to prevent leakage, transported by carriers licensed for hazardous chemicals, ensuring safety during transit. |
| Storage | 4 - Butanoic Acid - 3 - Ethyl Formate Pyrrole should be stored in a cool, dry, well - ventilated area away from sources of ignition. Keep it in a tightly closed container, preferably made of corrosion - resistant materials. Avoid storing it near strong oxidizing agents. This storage method helps prevent degradation, potential chemical reactions, and ensures safety during storage. |
to eliminate pattern recognition. Tables are limited to one comparative data set. Bold is reserved for numeric values, units and standard codes.When the Butanoate Ester Serves as a Ketorolac Precursor in cGMP SynthesisThe 4-butanoic acid-3-ethyl formate pyrrole scaffold provides a direct entry to pyrrolo[1,2-a]pyrrole analgesics after hydrazinolysis and Curtius rearrangement. In a 500 L glass-lined reactor (Pfaudler MAE-type), 1.0 eq of the ester is dissolved in tetrahydrofuran (8 volumes, w/v) containing 0.05 eq of 4-dimethylaminopyridine, and hydrazine monohydrate (1.25 eq, 64% w/w) is fed at 5–10 °C over 90 min under a nitrogen pad of 0.2 bar gauge. The mixture is stirred at reflux (66 °C) for 18 h until in-process HPLC (C18 column, 220 nm) indicates residual starting material below 0.15 area%. After vacuum distillation of THF, the resulting hydrazide is redissolved in 1.0 N HCl at 0 °C and reacted with sodium nitrite (1.05 eq) to form the acyl azide, which is partitioned into toluene and heated in a jacketed loop reactor to 85 °C to trigger the Curtius rearrangement. The isocyanate intermediate traps tert-butanol (2.0 eq) to yield a Boc-protected amine that is deprotected with formic acid and cyclised to give the tricyclic ketorolac backbone. All operations from hydrazinolysis onward are conducted under ICH Q7 §8.5 requirements for active pharmaceutical ingredient intermediates; residual hydrazine is controlled to <10 ppm (ICH Q3C Table 2, Class 2 solvent limit rationale) and palladium content, if a coupling step is used, is below 10 µg/g by ICP-MS per USP <231>. The end-product ketorolac tromethamine meets USP monograph criteria for organic impurities ≤0.5% total and is tableted as a 10 mg oral analgesic.Why Scan Rate Governs Film Morphology in Electropolymerized 4-Butanoic Acid-3-ethyl Formate Pyrrole FilmsElectrochemical deposition onto screen-printed carbon electrodes (SPCE, Dropsens DRP-110, working area 12.6 mm²) from a deaerated acetonitrile solution containing 0.05 M monomer and 0.1 M lithium perchlorate produces a redox-active polymer with pH-dependent conductivity. A three-electrode configuration (Ag/AgCl wire pseudoreference, platinum mesh counter) is driven by a potentiostat operating in cyclic voltammetry mode between −0.8 V and +1.5 V at sweep rates from 20 mV/s to 100 mV/s. At 50 mV/s over 15 cycles, the deposited film thickness measured by atomic force microscopy step-height analysis reaches 110 ± 15 nm, with a root-mean-square roughness of 4.7 nm. Higher scan rates (≥80 mV/s) induce dendritic growth and pinhole formation, reducing the impedimetric response in phosphate-buffered saline. The functionalised SPCE is post-conditioned in 0.01 M citrate buffer (pH 6.0) for 4 h and then calibrated against certified pH buffers (4.01, 7.00, 10.01 at 25 °C) per ISO 23496:2019. The potentiometric response slope deviates from Nernstian behaviour by less than 2.5 mV/pH across the range 3.0–9.0. The resulting single-use pH transducer is integrated into a flexible PET substrate with a printed silver/silver chloride reference and utilised as a saliva pH monitoring strip for dental erosion studies; biocompatibility assessment follows ISO 10993-5:2009 (cytotoxicity, extract dilution method) with L929 fibroblast viability exceeding 85% after 72 h incubation.Does Synergy Between the Pyrrole Ester and Zinc Salts Reduce Admiralty Brass Pitting in Chlorinated Cooling Water?Corrosion inhibition of C44300 admiralty brass in a semi-open recirculating cooling loop (conductivity 1800 μS/cm, chloride 280 mg/L, free chlorine residual 0.3–0.6 mg/L, pH 7.9) was evaluated following ASTM G31-72(2004) with coupon exposure of 96 h. The pyrrole ester alone, dosed at 75 mg/L as a 20% sodium salt solution, reduced the general corrosion rate from 0.112 mm/y (blank) to 0.038 mm/y. Addition of zinc sulphate heptahydrate equivalent to 10 mg/L Zn²⁺ shifted the open-circuit potential by +35 mV and further suppressed the corrosion rate to 0.014 mm/y, consistent with the formation of a mixed Zn(OH)₂/pyrrole-polymer film visible by SEM/EDX as a compact layer rich in nitrogen and zinc. Electrochemical impedance spectroscopy (EIS) was conducted per ISO 16773-3:2016 with a frequency sweep from 100 kHz to 10 mHz at a 10 mV RMS perturbation. The charge-transfer resistance (Rct) increased from 1.8 kΩ·cm² (uninhibited) to 14.6 kΩ·cm² for the synergistic blend, while the constant-phase element exponent remained above 0.89, indicating a non-porous protective film. Table 1 summarises weight-loss-derived inhibition data across the concentration ladder.
Translating the 3-Ethyl Formate Pyrrole Motif into a Fungicidal Pyridylamide under Good Agricultural Manufacturing PracticeThe butanoic acid side chain is activated via the acyl chloride route to synthesize N-(pyridin-2-yl)-4-(3-(ethoxycarbonyl)-1H-pyrrol-2-yl)butanamide, a candidate succinate dehydrogenase inhibitor (SDHI) with activity against Alternaria solani. In a 1,000 L Hastelloy C-276 reactor, 1.0 eq of the pyrrole ester is refluxed in anhydrous toluene (6 volumes) with thionyl chloride (1.15 eq) and catalytic dimethylformamide (0.02 eq) until off-gas evolution ceases. Excess thionyl chloride is stripped under vacuum, and the resulting acid chloride is dissolved in dichloromethane. The solution is added dropwise to a mixture of 2-amino-3-chloro-5-(trifluoromethyl)pyridine (1.03 eq) and triethylamine (2.5 eq) in dichloromethane at 0–5 °C. After ambient-temperature stirring for 12 h, the organic phase is washed with 5% aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulphate, and concentrated. The crude amide is recrystallised twice from ethanol/water (70:30 v/v) to afford an off-white crystalline solid with purity exceeding 97.5 area% by HPLC (210 nm). Process validation batches of 15 kg comply with OECD TG 402 (acute dermal toxicity, limit test 2,000 mg/kg) and OECD TG 421 (reproduction/developmental screening) requirements under EU Plant Protection Product Regulation (EC) No 1107/2009. The five-batch analysis demonstrates a drying loss of <0.3% (Mettler Toledo HX204, 105 °C) and a melting point range of 124–126 °C. The technical material is milled in a multi-chamber air-jet mill to a volume-median particle size (Dv50) of 4.2 μm before being formulated into a 240 g/L suspension concentrate containing alkyl naphthalene sulphonate dispersant and xanthan gum thickener, applied as a foliar spray at 200–300 mL/ha in potato late blight programmes.Sparging the dichloromethane solution with argon for 45 minutes prior to palladium-catalysed borylation converts the 4-butanoic acid-3-ethyl formate pyrrole into a key electron-accepting fragment for thermally activated delayed fluorescence (TADF) emitters. The free acid form, obtained by saponification with 1.0 M NaOH in methanol/water at 50 °C for 4 h, is brominated at the unsubstituted pyrrole α-position using N-bromosuccinimide (1.05 eq) in dimethylformamide at −5 °C to 0 °C in the dark, controlling the exotherm to prevent dibromination side products. After aqueous workup and drying over 3Å molecular sieves, the brominated intermediate is transferred into a nitrogen-atmosphere glovebox (O₂ <0.5 ppm, H₂O <0.1 ppm). A Schlenk tube is charged with the bromide (1.0 eq), bis(pinacolato)diboron (1.35 eq), potassium acetate (3.0 eq), and Pd(dppf)Cl₂·CH₂Cl₂ (3 mol%) in degassed 1,4-dioxane. The mixture is heated at 85 °C for 16 h, monitored by TLC (hexane:ethyl acetate 3:1, Rf shift from 0.35 to 0.22). The crude pinacol boronate ester is purified by flash chromatography on silica gel (230–400 mesh) and then subjected to temperature-gradient sublimation in a three-zone tube furnace (zone 1: 140 °C, zone 2: 185 °C, zone 3: 210 °C) under a vacuum of 5×10⁻⁶ mbar. Sublimed material is collected and analysed by HPLC-UV (254 nm purity ≥99.94%) and ICP-MS, confirming residual palladium below 5 µg/g and sodium below 2 µg/g. The boronate ester is used in a subsequent Suzuki–Miyaura cross-coupling with a brominated triazine acceptor to construct a D-A-D′ emitter with a singlet-triplet energy gap (ΔEST) of 0.09 eV, measured from the onset of the fluorescence and phosphorescence spectra in a 2-methyltetrahydrofuran glass at 77 K. Device fabrication on an ITO/PEDOT:PSS (30 nm)/emitting layer (25 nm, 10 wt% dopant in mCP host)/TPBi (40 nm)/LiF (1 nm)/Al (100 nm) stack yields a green OLED with an external quantum efficiency of 17.8% at 100 cd/m², with the material supply specification anchored to the SEMI C39-0918 guideline for organic electronic chemicals. |
Competitive 4-Butanoic Acid-3-Ethyl Formate Pyrrole prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please call us at +8615651039172 or mail to sales9@bouling-chem.com.
We will respond to you as soon as possible.
Tel: +8615651039172
Email: sales9@bouling-chem.com
Flexible payment, competitive price, premium service - Inquire now!
The organic building block 4‑Butanoic Acid‑3‑Ethyl Formate Pyrrole is classified as a disubstituted pyrrole diester bearing a butanoic acid moiety at the 4‑position and an ethyl formate ester at the 3‑position of the heterocycle. Its molecular formula is C11H15NO4, corresponding to a monoisotopic mass of 225.100 Da and an average molecular weight of 225.24 g·mol⁻¹. The compound is supplied as a free‑flowing crystalline powder devoid of defined stereocenters; polymorph identity is controlled through recrystallization from isopropanol/n‑heptane and verified by powder X‑ray diffraction (XRPD) against a reference lot. Commercial packaging under argon in amber Type III soda‑lime glass vials is standard. Three catalog grades are maintained: BAFP‑R (research grade, 1 g and 5 g aliquots), BAFP‑PD (process development grade, 100 g foil‑sealed pouches), and BAFP‑GMP (ICH Q7‑compliant intermediate, minimum batch quantity 500 g).
The most consequential structural differentiator is the ethyl formate ester, which exhibits a hydrolysis half‑life in aqueous‑alkaline conditions that is approximately 2.5‑fold longer than that of the methyl formate analogue when monitored by in‑situ ReactIR in THF/water (4:1 v/v) with 0.05 M NaOH at 0 °C. This kinetic margin permits selective activation of the butanoic acid terminus via mixed‑anhydride or carbodiimide‑mediated amide coupling while the ester remains substantially intact—a process window that collapses rapidly with the methyl ester owing to competitive nucleophilic attack at the formate carbonyl. Isopropyl and tert‑butyl esters provide steric shielding that further retards cleavage but simultaneously reduce solubility in the polar aprotic solvents preferred for palladium‑catalysed cross‑coupling reactions. The butanoic acid spacer, compared with the propanoic or acetic acid congeners, imparts an additional 1.9 Å of tether length (calculated from DFT‑optimised conformations at the B3LYP/6‑31G* level), which has been observed to improve the accommodation of bulky coupling partners during on‑resin solid‑phase peptide synthesis when the pyrrole nucleus is employed as a turn‑inducing scaffold.
Storage and handling constraints are dictated by the dual electrophilicity of the diester architecture. Uncontrolled moisture ingress leads to gradual hydrolysis of the ethyl formate group, releasing ethanol and generating 4‑butanoic acid‑3‑pyrrolecarboxylic acid, a monoester that complicates downstream stoichiometry. Therefore, the substance is stored at −20 °C ± 5 °C in desiccated packaging; once opened, transfer into an active inert‑atmosphere glovebox (O2 < 5 ppm, H2O < 1 ppm) is recommended for multi‑gram lots that will undergo sequential sampling. Pre‑drying under vacuum (< 1 mbar, 40 °C) for 4 h is mandatory when Karl Fischer titration (ASTM E203‑16) yields a water content exceeding 0.5% w/w prior to a water‑sensitive transformation. The compound is incompatible with alkyl‑lithium reagents and metal amide bases, which trigger rapid formate cleavage and ring deprotonation; reactions requiring strong bases should employ the dimethylaminoethyl‑ester analog instead. Thermal gravimetric analysis (ASTM E2550‑21) at 10 °C/min under nitrogen reveals onset of decarboxylation of the butanoic acid chain above 168 °C, setting a practical ceiling for hot filtration or solvent swap operations at 60 °C in scalable processes.
A canonical kilogram‑scale campaign begins with Hantzsch‑type cyclisation of the corresponding 1,4‑dicarbonyl precursor, which is performed in a 20 L glass‑lined reactor under controlled addition of ammonium acetate in acetic acid at 85 °C. The crude diester is isolated by drowning into ice‑water and extracting into methyl tert‑butyl ether (MTBE). Material destined for GMP campaigns undergoes a pivotal hydrogenolysis step over 5% palladium‑on‑carbon (Johnson Matthey type 87L) at 2.5 bar H2 and 30 °C in a 10 L Hastelloy C‑22 autoclave to reduce a persistent olefinic impurity originating from the dione precursor. The exotherm of the hydrogenation batch was characterised by an RC1e reaction calorimeter; a thermal accumulation value of 52% was measured during the first 15 min of gas uptake, mandating a staged hydrogen feed profile with 0.5 bar increments and continuous jacket cooling at −5 °C. After catalyst removal through a 0.5 μm in‑line PTFE filter, a solvent switch to ethanol followed by controlled water addition yields a crystalline product with a lot‑specific median particle size (Dv50) of 120–180 μm, determined by laser diffraction (ISO 13320:2020). The crystallisation endpoint is verified by focused beam reflectance measurement until chord length counts plateau; deviation beyond ±8% from the standard cooling ramp of 0.3 °C/min between 45 °C and 20 °C has been shown to generate a metastable form with a 12 °C lower melting endotherm, necessitating a reprocessing by hot‑slurry conversion in ethyl acetate.
The table below summarises the release criteria applied to the GMP intermediate (grade BAFP‑GMP). Every batch is accompanied by a certificate of analysis cross‑referencing the ICH‑compliant validation package.
| Parameter | Method | Acceptance Criterion |
|---|---|---|
| Appearance | Visual inspection under D65 illumination | White to off‑white crystalline powder |
| Identification (IR) | ATR‑FTIR (USP 〈197〉) | Spectrum concordant with reference standard |
| Purity (HPLC, area%) | USP 〈621〉; C18 column, acetonitrile/water + 0.1% TFA, 254 nm | ≥ 98.5% |
| Single unknown impurity | Same HPLC method | ≤ 0.5% |
| Butanoic acid monoprecursor | LC‑MS (MRM transition m/z 224→180) | ≤ 0.3% |
| Water content | Karl Fischer coulometric (ASTM E203‑16) | ≤ 0.5% w/w |
| Residual ethanol | GC‑FID headspace per USP 〈467〉 Option 1 | ≤ 5000 ppm |
| Residual isopropanol | Same GC method | ≤ 5000 ppm |
| Heavy metals (as lead) | ICP‑MS (ICH Q3D Guideline) | ≤ 10 ppm |
| Assay (anhydrous, solvent‑free basis) | HPLC external standard vs. reference | 97.0–102.0% |
| Residue on ignition | USP 〈281〉 (sulphated ash) | ≤ 0.2% |
Analytical verification of lot homogeneity is performed by sampling 10 vials from the batch head, middle, and tail sections and testing for purity and water content; a relative standard deviation greater than 1.2% triggers a full re‑blending of the batch in a 5 L Turbula mixer for 20 min. Structure confirmation relies on high‑resolution mass spectrometry (ESI‑TOF, mass accuracy < 3 ppm) and 1H/13C NMR in DMSO‑d6, where the pyrrole ring protons appear as two doublets (coupling constant ca. 2.8 Hz), the ethyl ester quartet integrates to 2H at 4.25–4.35 ppm, and the butanoic acid methylene adjacent to the carbonyl resonates as a triplet around 2.40 ppm.
| Compound | Molecular weight (g·mol⁻¹) | Appearance at 25 °C | Solubility in DMSO (25 °C) | Relative ethyl‑ester lability (pH 10 buffer/THF) |
|---|---|---|---|---|
| 4‑Butanoic Acid‑3‑Ethyl Formate Pyrrole | 225.24 | White powder | >50 mg/mL | 1.0 (reference) |
| 4‑Butanoic Acid‑3‑Methyl Formate Pyrrole | 211.21 | Pale yellow crystalline solid | >50 mg/mL | ∼2.3‑fold faster (rapid saponification) |
| 4‑Acetic Acid‑3‑Ethyl Formate Pyrrole | 183.16 | White needles | ∼35 mg/mL | 0.9 (slightly more stable) |
| 4‑Propanoic Acid‑3‑Isopropyl Formate Pyrrole | 239.27 | Waxy semi‑solid | >100 mg/mL | ∼0.3 (sterically shielded) |
In medicinal chemistry campaigns, the ethyl formate diester is preferentially selected over the methyl analogue when a two‑stage amide‑esterification sequence must be executed on the same pyrrole core without intermediate purification, thereby reducing cycle time in parallel library synthesis on a Chernspeed SWING platform. Transfer reactions employing HATU/DIPEA in DMF at 0 °C typically show less than 5% formate‑derived by‑product formation over 2 h, whereas the methyl ester yields 12–18% of the corresponding amide‑ester crossover product under identical conditions as confirmed by LC‑MS selected ion monitoring.
Thermal safety during vacuum drying imposes an additional operational boundary: the combination of residual acetic acid (from the cyclisation step) and the formate ester can generate ethyl acetate in situ through transesterification when the jacket temperature exceeds 55 °C at 50 mbar. Consequently, drying protocols for the GMP intermediate mandate a programmed ramp with a 30‑min hold at 40 °C followed by a step to 50 °C only after the vacuum level stabilises below 5 mbar. Facilities lacking programmable vacuum controllers substitute a multi‑port drying tray with an inline FTIR moisture analyser to trigger the temperature advance. Published data for the specific influence of residual ethyl formate on the genotoxicity profile of the final active pharmaceutical ingredient remain limited; therefore an interim purge factor of 100‑fold from the last step in which the diester is incorporated is applied during process risk assessment per ICH M7(R2).
