(1S,3Ar,6As)-Tert-Butyl Octahydrocyclopenta[C]Pyrrole-1-Carboxylate Oxalate
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HS Code |
640327 |
As an accredited (1S,3Ar,6As)-Tert-Butyl Octahydrocyclopenta[C]Pyrrole-1-Carboxylate Oxalate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of (1S,3Ar,6As)-Tert - Butyl Octahydrocyclopenta[c]Pyrrole - 1 - Carboxylate Oxalate in sealed chemical - grade package. |
| Shipping | (1S,3Ar,6As)-Tert - Butyl Octahydrocyclopenta[c]Pyrrole - 1 - Carboxylate Oxalate is shipped with utmost care. Packed in a well - sealed, corrosion - resistant container, it's transported under controlled conditions to prevent degradation and ensure safe delivery. |
| Storage | (1S,3Ar,6As)-Tert - Butyl Octahydrocyclopenta[c]Pyrrole - 1 - Carboxylate Oxalate should be stored in a cool, dry place. Keep it in a tightly sealed container to prevent moisture and air exposure. Avoid storage near heat sources or direct sunlight, as these may cause decomposition. Store away from incompatible substances to ensure chemical stability. |
A Protected Bicyclic Proline Surrogate in GLP-1 Agonist Process ChemistryIn the convergent synthesis of peptidic glucagon-like peptide-1 (GLP-1) receptor agonists, incorporation of conformationally constrained amino acid residues into the backbone has been correlated with enhanced proteolytic stability and prolonged in vivo half-life. The octahydrocyclopenta[c]pyrrole scaffold, when presented as the (1S,3aR,6aS)-tert-butyl carboxylate oxalate salt, functions as a masked proline isostere in which the cyclopentane annulation restricts pseudorotation of the pyrrolidine ring. On pilot-plant-scale solid-phase peptide synthesis (SPPS) rigs equipped with 500–1000 mmol capacity polypropylene reactors and recirculating N-methyl-2-pyrrolidone (NMP) solvent delivery, the oxalate salt is neutralized in situ with N,N-diisopropylethylamine (DIPEA, 2.2–2.5 molar equivalents relative to the oxalate counterion) immediately prior to coupling. Activation via 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 1.05 eq) in anhydrous NMP at 0–5°C for a 90-second pre-activation window yields an acylated species that is coupled to the resin-bound deprotected N-terminus over a 20-minute recirculation cycle. Coupling efficiency, monitored by Kaiser test at each cycle, typically exceeds 98.5%; incomplete coupling triggers a mandatory capping step with acetic anhydride/pyridine (1:1 v/v) to prevent deletion sequence impurities that would co-elute during preparative reversed-phase HPLC purification on C18 stationary phases (10 μm, 250 × 50 mm axial compression columns) with 0.1% trifluoroacetic acid/acetonitrile gradients. The tert-butyl carbamate (Boc) protecting group remains intact throughout chain elongation and is cleaved during the global resin cleavage–deprotection cocktail (TFA/triisopropylsilane/water, 95:2.5:2.5 v/v/v, 2.5 h at 25°C) alongside side-chain protecting groups. Crude peptide purity exceeding 75% by analytical HPLC (C18, 214 nm) is routinely achieved before chromatographic polishing. ICH Q7 Q7A Good Manufacturing Practice for Active Pharmaceutical Ingredients governs all processing steps from pilot-scale campaigns forward; master batch records document the exact stoichiometry of oxalate neutralization because residual oxalic acid in the coupling solution depresses the effective concentration of DIPEA and retards acylation kinetics. Terminal drug substances incorporating this constrained building block include injectable GLP-1 formulations dispensed in multi-dose pre-filled pens containing 1.5–3.0 mL of sterile aqueous solution at pH 7.4 with phenol or m-cresol preservative systems.What Are the Crystallization Solvent Requirements for Kilogram-Scale Isolation of the Free Amine?The oxalate salt is the preferred physical form for ambient-temperature storage and transport because the free base of (1S,3aR,6aS)-tert-butyl octahydrocyclopenta[c]pyrrole-1-carboxylate exhibits a measurable tendency toward carbamate migration when exposed to adventitious moisture in non-climate-controlled warehouses. Conversion from oxalate to free amine is a prerequisite for all peptide coupling applications, and the workup procedure adopted at production scale differs materially from bench-scale protocols described in medicinal chemistry literature. A 50-kg batch of oxalate is suspended in ethyl acetate (8 volumes, pre-filtered through 0.45 μm PTFE membrane) and washed with saturated aqueous sodium bicarbonate (2 × 3 volumes) in a glass-lined 800 L reactor fitted with a retreat-curve impeller operating at 90 rpm. Each wash cycle is agitated for 30 minutes at 20–23°C; phase separation is assisted by addition of sodium chloride (5 wt% relative to aqueous phase) when emulsion persists beyond 15 minutes. The organic phase is dried over anhydrous sodium sulfate (1.5 kg per 100 L of ethyl acetate) for a minimum of 4 hours with intermittent stirring, filtered through a 5 μm sintered stainless steel in-line filter, and concentrated under reduced pressure (50–60 mbar, jacket temperature not exceeding 35°C) in a wiped-film evaporator to prevent thermal degradation of the Boc group. The residual oil is crystallized from n-heptane/tert-butyl methyl ether (4:1 v/v, 5 volumes) with a controlled cooling ramp: 50°C to 25°C at 0.3°C/min, then 25°C to -5°C at 0.1°C/min. Nucleation is induced by seeding with 0.5 wt% micronized crystals of the free amine (sieved through 100 μm mesh) at 38°C during the initial cooling phase. Yield of free amine as a white crystalline solid is consistently 88–92% with chemical purity ≥ 99.0% by GC-FID (Agilent DB-5, 30 m × 0.32 mm, 0.25 μm film, oven program 80–280°C at 10°C/min) and enantiomeric excess ≥ 99.5% by chiral HPLC (Chiralpak AD-H, 250 × 4.6 mm, n-hexane/isopropanol 90:10, 1.0 mL/min, 210 nm). Residual oxalic acid content, quantified by ion chromatography (Dionex IonPac AS11-HC, suppressed conductivity detection), must be below 0.05% w/w before the free amine is released for peptide synthesis; batches failing this specification are re-dissolved in ethyl acetate and subjected to an additional bicarbonate wash. The isolated free amine is packaged in double polyethylene liners inside fiber drums purged with dry nitrogen and stored at 2–8°C with a retest date of 12 months assigned after accelerated stability studies conducted per ICH Q1A(R2) guidelines at 40°C/75% RH for 6 months.Sub-nanomolar inhibition of the Hepatitis C Virus (HCV) NS3/4A serine protease by macrocyclic acylsulfonamide inhibitors is contingent upon the precise spatial orientation of the P2 proline moiety within the enzyme’s S2 subsite. Substitution of natural L-proline with the (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate fragment introduces a cyclopentane ring that occupies a hydrophobic cleft defined by residues Arg155, Ala156, and Val158, displacing a conserved water molecule observed in crystallographic structures of the apo enzyme (PDB entries 3LOX, 4K8B). The oxalate salt is neutralized with excess triethylamine (3.0 eq) in dichloromethane at -10°C, and the resulting free amine is coupled to a pre-formed P3-P2 dipeptide acid using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.2 eq) and 1-hydroxybenzotriazole hydrate (HOBt·H₂O, 1.3 eq). This carbodiimide-mediated coupling is conducted in anhydrous dichloromethane at 0°C over 16 hours under an argon atmosphere in a 100 L Hastelloy C-276 reactor; moisture ingress above 50 ppm in the headspace, monitored by a dew-point transmitter, triggers automatic termination of the batch because HOBt esters undergo rapid hydrolysis that generates des-acyl intermediate as the primary impurity. After aqueous workup (1 N HCl, saturated NaHCO₃, brine) and solvent swap to acetonitrile, the linear tripeptide precursor is isolated by silica gel chromatography (eluent: ethyl acetate/hexane, 3:7 to 1:1 gradient) and crystallized from isopropyl acetate to obtain material of > 99.5% diastereomeric purity. The Boc group is removed with HCl gas in dioxane (4 M, 10 eq, 2 h at 25°C), and the resulting amine hydrochloride is telescoped directly into the macrocyclization reaction: ring-closing metathesis (RCM) catalyzed by Hoveyda-Grubbs Catalyst™ M720 (0.5 mol% in toluene, 80°C, 0.005 M substrate concentration) forms a 15-membered macrocyclic olefin, subsequently hydrogenated over 10% Pd/C (5 wt%, 1 atm H₂, ethanol) to the saturated lactam. Oxidation of the P1 vinylcyclopropane to the corresponding acylsulfonamide proceeds through a two-step sequence (Dess-Martin periodinane then Pinnick oxidation) and final coupling with cyclopropylsulfonamide using 1,1'-carbonyldiimidazole (CDI, 1.5 eq) in THF at 65°C yields the active pharmaceutical ingredient. ICH Q3C (R8) residual solvent limits apply to the final recrystallization from ethanol/water (7:3 v/v); headspace GC-MS quantifies residual dichloromethane (< 600 ppm), acetonitrile (< 410 ppm), and isopropyl acetate (< 5000 ppm) in the release specification. Finished dosage forms are film-coated tablets containing 100 mg of the HCV protease inhibitor co-formulated with ritonavir 100 mg as a pharmacokinetic booster in a fixed-dose combination product dispensed in HDPE bottles with child-resistant closures and desiccant canisters. Constrained Dipeptidyl Peptidase-4 Inhibitor Fragment: Reaction Calorimetry and Boc Deprotection KineticsA sub-class of dipeptidyl peptidase-4 (DPP-4) inhibitors incorporates a fused bicyclic pyrrolidine at the P2 position to achieve extended residence time within the DPP-4 active site, as demonstrated by co-crystal structures showing the cyclopentane ring in van der Waals contact with Tyr547 and Trp629 in the S2 extensive subsite. Manufacturing-scale introduction of the (1S,3aR,6aS)-configured octahydrocyclopenta[c]pyrrole fragment begins with the oxalate salt, which is converted to the free amine in a continuous-flow neutralization module to circumvent batch-wise phase separation bottlenecks. A solution of oxalate in 2-methyltetrahydrofuran (2-MeTHF, 0.5 M, pre-dried over 3Å molecular sieves) and aqueous potassium carbonate (2 M, 2.5 equivalents) is metered into a Corning® Advanced-Flow™ G1 silicon carbide reactor (module volume 10 mL per plate, 4 plates in series) with a combined flow rate of 20 mL/min at 25°C and 3 bar back-pressure. Residence time is 30 seconds; in-line IR spectroscopy (Mettler Toledo ReactIR™ 15 with DiComp diamond ATR probe, monitoring the carbonyl stretch at 1720 cm⁻¹ for the oxalate C=O) confirms complete neutralization. The organic stream is separated via a Zaiput continuous liquid-liquid separator (0.5 μm PTFE membrane), dried by passage through a column of anhydrous magnesium sulfate, and concentrated in a wiped-film evaporator (60°C, 50 mbar). The free amine is then coupled to a β-amino acid fragment using propanephosphonic acid anhydride (T3P®, 50 wt% in ethyl acetate, 1.5 eq) and pyridine (3.0 eq) in ethyl acetate at 0–5°C; T3P is selected over HATU for this specific coupling because the β-amino acid substrate undergoes competitive epimerization at the α-position under carbodiimide activation. Reaction completion is verified by in-process HPLC (C18, phosphate buffer pH 7.0/acetonitrile, 210 nm) within 8 hours. After standard aqueous workup, the Boc-protected dipeptide intermediate is isolated as a foam and subjected to Boc removal using methanolic HCl (1.25 M, 8 eq HCl, 20°C, 3 h) in a 200 L glass-lined reactor. Reaction calorimetry data (Mettler Toledo RC1e, isothermal mode at 20°C) records a heat flow of -145 kJ/mol of substrate during the deprotection, with a maximum heat release rate of 28 W/kg observed during the initial 15-minute dosing period. These data inform the jacket cooling capacity specification: a 200 L reactor with a heat transfer coefficient of 250 W/m²·K and a jacket temperature of -10°C provides adequate thermal safety margin per the Stoessel criticality classification (class 3, target temperature 20°C, MTSR 35°C, TD24 of the deprotected amine·HCl is 168°C by DSC, resulting in a time-to-maximum-rate of > 24 h). The deprotected amine is telescoped as a hydrochloride salt into the final amide bond formation with a substituted quinazoline acid chloride, and the crude DPP-4 inhibitor is recrystallized from ethanol/water to obtain polymorph Form I (confirmed by XRPD, characteristic peaks at 2θ = 9.8°, 14.2°, 18.7°, Cu Kα radiation). ICH Q3D Guideline for Elemental Impurities requires control of palladium (limit: oral, PDE 100 μg/day) if hydrogenation is used elsewhere in the route; analysis by ICP-MS (Agilent 7800) quantifies Pd at < 1 ppm in the final API. Q6A specifications include assay by HPLC (98.0–102.0%), enantiomeric purity ≥ 99.0%, and residual solvents meeting USP <467> Option 1 limits. The commercial drug product is an immediate-release tablet containing 25 mg or 100 mg of the DPP-4 inhibitor as a phosphate salt, formulated with microcrystalline cellulose (Avicel PH-102), croscarmellose sodium, magnesium stearate, and Opadry® II film coating, packaged in aluminum/aluminum blister cavities.Fragment-based drug discovery screening against the BRD4 bromodomain (Kd determined by isothermal titration calorimetry in 50 mM HEPES pH 7.5, 150 mM NaCl, 2 mM TCEP at 25°C) has identified the octahydrocyclopenta[c]pyrrole ring system as a privileged fragment for displacing the acetyl-lysine binding pocket. The (1S,3aR,6aS)-tert-butyl carboxylate oxalate serves as a starting material for elaboration to a bi-aryl BET bromodomain inhibitor series. In a process chemistry route optimized for 5–10 kg batch size in a preclinical manufacturing setting, the oxalate (1.0 eq) is neutralized with saturated aqueous sodium carbonate and extracted into dichloromethane. The free amine is acylated with 4-chlorobenzoyl chloride (1.05 eq) in dichloromethane in the presence of triethylamine (2.5 eq) at 0°C; the exotherm is moderated by slow addition of the acid chloride over 45 minutes while the jacket temperature is maintained at -5°C. The resulting benzamide intermediate is purified by silica gel plug filtration (ethyl acetate/hexane 1:2) with a typical recovery of 95% and purity ≥ 97% by HPLC. Subsequent Suzuki-Miyaura cross-coupling with a boronic acid partner bearing a methyl ester substituent is performed under standard conditions: Pd(dppf)Cl₂·CH₂Cl₂ (2 mol%), potassium carbonate (3 eq) in dioxane/water (4:1, degassed by three freeze-pump-thaw cycles on development scale or by subsurface nitrogen sparging on production scale) at 85°C for 12 h. The biphenyl ester is saponified with lithium hydroxide monohydrate (3 eq) in THF/water (3:1) at 25°C over 6 h; the carboxylic acid is isolated by acidification to pH 3 (2 N HCl), extraction into ethyl acetate, and trituration with n-heptane. Final amide coupling with methylamine hydrochloride using HATU (1.1 eq) and DIPEA (3.0 eq) in DMF at 0°C yields the BRD4 inhibitor scaffold. The Boc protecting group is retained until the final step to facilitate intermediate purification and is removed with TFA/DCM (1:1, 2 h, 25°C) to expose the secondary amine, which is subsequently converted to the hydrochloride salt with HCl/Et₂O for improved solubility in biological assay media. Analytical release testing of the preclinical batch includes: HPLC purity (≥ 95% at 254 nm), ¹H NMR (DMSO-d₆, 500 MHz, integration consistent with ≥ 95% purity), and HRMS (ESI+, [M+H]⁺ within 3 ppm of theoretical mass). Environmental, Health, and Safety considerations under REACH Regulation (EC) No. 1907/2006 apply to the dichloromethane used in the route; exposure limits are monitored with Dräger tubes (short-term exposure limit 100 ppm, time-weighted average 50 ppm per 8-hour period), and recovery by distillation is implemented with a target solvent recovery rate of 85% to meet waste reduction commitments. Integrin αvβ6 Inhibitor Synthesis Incorporating a Bicyclic β-Turn MimeticConformational restriction of the Arg-Gly-Asp (RGD) recognition sequence in integrin αvβ6 antagonists has been achieved by replacing the central glycine residue with the (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate scaffold. This substitution enforces a torsion angle (φ ≅ -65°, ψ ≅ 150° as determined by ¹H NMR coupling constant analysis in D₂O and corroborated by Monte Carlo conformational searching in MacroModel 12.5) that pre-organizes the Arg and Asp side chains for simultaneous coordination to the Mg²⁺ ion in the metal ion-dependent adhesion site (MIDAS) and the adjacent synergy site. The synthetic sequence at multi-hundred-gram scale initiates with oxalate neutralization using polymer-supported 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (PS-BEMP, 2.2 eq, 2.3 mmol/g loading) in anhydrous tetrahydrofuran at ambient temperature for 30 minutes with orbital shaking (120 rpm) in an SPPS-style batch reactor. PS-BEMP is preferred over soluble amine bases because it eliminates a chromatographic purification step: filtration through a 70 μm polypropylene frit and THF rinses (3 × 2 reactor volumes) provide the free amine in > 98% recovery. The filtrate is concentrated and the residue is dissolved in DMF for immediate coupling with Fmoc-Arg(Pbf)-OH (1.1 eq) activated by HATU (1.1 eq) and 2,4,6-collidine (2.5 eq); collidine is selected over DIPEA to minimize racemization at the Arg α-carbon, monitored by the diastereomeric excess (de) of the product determined by chiral HPLC after Fmoc deprotection (20% piperidine/DMF, 2 × 10 min). The dipeptide is crystallized from isopropanol/water (1:1) to achieve > 99% de. After Fmoc removal and coupling with N-α-Fmoc-N-β-allyloxycarbonyl-L-2,3-diaminopropionic acid as an aspartic acid mimetic, the fully protected linear precursor is subjected to on-resin cyclization for analogues or solution-phase macrolactamization (diethyl cyanophosphonate, N-methylmorpholine, DMF, 0.01 M substrate concentration to suppress dimerization, 16 h at 25°C) to form a 14-membered ring. Global deprotection with Reagent K (TFA/phenol/water/thioanisole/ethanedithiol, 82.5:5:5:5:2.5 v/v/v/v/v, 3 h, 25°C) followed by precipitation from cold diethyl ether and preparative HPLC (C18, 0.1% TFA/acetonitrile mobile phase, 220 nm detection) yields the cyclic peptide as the TFA salt. Counterion exchange to acetate is effected by ion-exchange chromatography (Dowex 1X8, acetate form, eluted with water) to improve lyophilization behavior and reduce residual TFA to < 0.1% by ion chromatography. Terminal filtration through a 0.22 μm PVDF membrane into sterile Type I borosilicate glass vials and lyophilization produces the injectable drug product, which is reconstituted with Water for Injection USP prior to intravenous administration. Shelf-life stability studies at 5°C ± 3°C per ICH Q5C for biotechnology-derived products guide a 24-month retest period; aggregate formation is monitored by size-exclusion HPLC (TSKgel G2000SWXL, phosphate-buffered saline pH 7.4, 0.5 mL/min, 214 nm), with a specification of ≤ 2.0% high-molecular-weight species. The finished product is an intravenous infusion concentrate containing 10 mg/mL of the cyclic peptide as acetate salt in a 5 mL single-dose vial with a bromobutyl rubber stopper and aluminum flip-off seal.Residual Palladium Specification in a Late-Stage Suzuki Coupling Toward a Clinical Triazole AntifungalA structural derivative of the octahydrocyclopenta[c]pyrrole core, when N-functionalized with a 2,4-difluorophenyl-1,2,3-triazole moiety via copper-catalyzed azide-alkyne cycloaddition (CuAAC), has demonstrated potent inhibition of fungal lanosterol 14α-demethylase (CYP51) in Candida auris isolates with FLZ MIC50 values of 0.06 μg/mL. The synthetic route positions the (1S,3aR,6aS)-tert-butyl carboxylate oxalate as the source of the chiral bicyclic amine, which is converted to the free amine with aqueous NaOH (5 N, 4 eq) and extracted into toluene. N-Alkylation with propargyl bromide (1.1 eq, 80 wt% in toluene, stabilized with MgO) in acetonitrile in the presence of anhydrous potassium carbonate (3 eq, 45°C, 18 h) installs the alkyne handle. After filtration of inorganic salts through a Celite pad and solvent exchange to THF, the CuAAC reaction is performed with 2,4-difluorophenyl azide (1.0 eq, prepared in situ from 2,4-difluoroaniline via diazotization with NaNO₂ in 6 N HCl/TFA and sodium azide at 0°C) catalyzed by copper(I) iodide (10 mol%) and N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA, 15 mol%) in THF at 25°C for 6 h under nitrogen. The triazole product is isolated after extractive workup with ethyl acetate and 10% aqueous NH₄OH (to remove copper salts), followed by silica gel chromatography (gradient: ethyl acetate in hexane, 30% to 70%). A subsequent Suzuki-Miyaura cross-coupling with 4-cyanophenylboronic acid pinacol ester (1.3 eq) is catalyzed by Pd(OAc)₂ (1 mol%) and SPhos (2 mol%) in toluene/water (3:1) with potassium phosphate tribasic (2 eq) at 85°C for 8 h under rigorous exclusion of oxygen (subsurface nitrogen sparging at 0.5 L/min per liter of reaction volume for 45 minutes before catalyst addition). The Boc group is removed with methanesulfonic acid (3 eq) in dichloromethane at 0°C; methanesulfonic acid is preferred over TFA when the target salt form is the mesylate, providing a convergent telescoped step. The crude mesylate salt is crystallized from ethanol/ethyl acetate (1:3) with a hot filtration step to remove insoluble palladium residues. Residual palladium is controlled to ≤ 10 ppm per the PDE of 100 μg/day for oral administration (ICH Q3D, Table 4.1, Class 1B element); analysis by ICP-MS (Agilent 7900 with collision cell in He mode, m/z 105, 106, 108 monitored for Pd, internal standard indium at m/z 115) on dissolved API samples (microwave digestion in concentrated HNO₃, diluted with 2% HNO₃ to 10 mL final volume) consistently achieves a limit of quantitation of 0.1 ppm. If residual Pd exceeds 10 ppm, the batch is reworked by treatment with N-acetyl-L-cysteine (2 eq in water, 50°C, 1 h) to complex soluble Pd species, followed by filtration through a 0.45 μm activated carbon cartridge (3M™ Zeta Plus™ BC series). The final mesylate salt is milled (FitzMill L1A, knives forward, medium speed, 0.020-inch screen) to achieve particle size distribution D90 of 150 μm for uniformity of dosage units per USP <905>. Tablets containing 150 mg of the triazole antifungal are manufactured by direct compression and coated with Opadry® AMB for moisture protection, packaged in induction-sealed HDPE bottles. USP <62> tests for objectionable microorganisms (Escherichia coli, Salmonella species, Pseudomonas aeruginosa, Staphylococcus aureus) are negative per 1 g sample. |
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| Property | (1S,3aR,6aS) Oxalate Salt | Free Base | Hydrochloride Salt |
|---|---|---|---|
| Appearance | White crystalline solid | Pale yellow oil | White hygroscopic solid |
| Melting/Decomposition point | 138–142 °C (dec) | Not observed below −20 °C | 155–160 °C (dec) |
| Solubility in DMF | ≥50 mg/mL | Miscible | ≥45 mg/mL |
| Weight gain at 55 % RH/4 h | ＋0.8 % | ＋3.2 % (deliquescent) | ＋5.1 % |
| Typical purity (HPLC) | ≥98.5 % | 92–96 % | 97.0–99.0 % |
| Handling suitability in 20‑L reactors | Direct solid addition through charge port | Requires solvent flush of weigh vessel | Addition under nitrogen purge recommended |
| Test parameter | Method reference | Acceptance criterion |
|---|---|---|
| Assay (non‑aqueous titration) | Perchloric acid in glacial acetic acid | 97.0–102.0 % |
| Purity (HPLC) | Area‑%, C18, 210 nm, ACN/H₂O with 0.1 % TFA | ≥98.5 % |
| Chiral purity | Chiralpak IA, heptane/ethanol/0.1 % DEA | ≤1.0 % opposite enantiomer |
| Water content | USP <921> Method Ⅰc | ≤0.3 % |
| Residual solvents | USP <467> Method Ⅳ | Ethyl acetate ≤5000 ppm; hexane ≤290 ppm |
| Oxalic acid content | Ion chromatography, Dionex AS11-HC | 28.5–29.5 % w/w |
| Specific rotation (free base) | Ph.Eur. 2.2.7, c=1.0, MeOH | [α]D20 = −48.0° ± 2.0° |
