(3R,4R)-Tert-Butyl 3-Amino-4-Hydroxypyrrolidine-1-Carboxylate

Moxifloxacin Side-Chain Condensation — A Thermally Sensitive Amide Coupling Workflow

In the industrial preparation of moxifloxacin hydrochloride monohydrate, the (3R,4R)-tert-butyl 3-amino-4-hydroxypyrrolidine-1-carboxylate entity functions as the chiral side-chain precursor that delivers the stereochemical signature of the final API. The downstream process begins with quantitative Boc-deprotection under anhydrous HCl in isopropanol at 0–5°C, yielding the corresponding amino alcohol hydrochloride with retention of the trans-configuration. This deprotected intermediate is then coupled to the 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid core via a mixed carbonic anhydride method utilising ethyl chloroformate and N-methylmorpholine in acetone at –15°C to –5°C. The molar ratio of side-chain to quinolone core is typically controlled at 1.05:1.00, with the slight excess compensating for residual moisture-induced hydrolysis. Deviations beyond 1.12 equivalents trigger a competing O-acylation pathway at the 4-hydroxyl position, generating a regioisomeric impurity that co-elutes with the desired product under standard reversed-phase HPLC conditions (C18, acetonitrile/phosphate buffer pH 2.8). Production-scale batches processed in glass-lined reactors with jacket cooling capacity of at least 3,500 W/m²·K routinely achieve coupling yields of 82–86% after crystallisation from ethanol/water (7:3 v/v).The regulatory framework governing this transformation includes ICH Q7, Section 8.3 (critical process parameters), EMEA/CHMP/QWP/2835/00 for active substance manufacture, and FDA 21 CFR Part 211.110 for in-process controls. Residual palladium from the quinolone core synthesis must remain below 10 ppm as determined by ICP-MS per USP <233> before coupling, since Pd(0) species catalyse pyrrolidine ring-opening under the acidic workup conditions. Terminal product specifications conform to Ph. Eur. monograph 2254 for moxifloxacin hydrochloride, which mandates NMT 0.10% of the 8-ethoxy analogue (a process-related impurity originating from ethanol-mediated trans-etherification during final recrystallization). The finished dosage form is moxifloxacin hydrochloride monohydrate tablets and infusion solutions, both requiring protection from light owing to the photolability of the C-8 methoxy substituent.

Why Does the C-4 Hydroxyl Configuration Destabilise Nemonoxacin Polymorph A?

The non-fluorinated quinolone nemonoxacin, approved in Taiwan and China for community-acquired pneumonia, incorporates the identical (3R,4R) absolute configuration at its pyrrolidine side chain. The free base of nemonoxacin is synthesised via direct nucleophilic aromatic substitution between the deprotected amino alcohol and the 7-halo-1-(2,4-difluorophenyl)-4-oxo-1,8-naphthyridine-3-carboxylic acid scaffold, employing K₂CO₃ in DMSO at 70–75°C for 16 hours. The Boc-protected precursor is introduced at a molar loading of 1.15–1.25 equivalents relative to the naphthyridone electrophile because the unprotected C-4 hydroxyl consumes approximately 8–12 mol% of the reagent in a competing intramolecular cyclisation that forms a fused morpholine by-product when the reaction is aged beyond 20 hours. This side reaction exhibits Arrhenius behaviour with an activation energy of 72 ± 4 kJ/mol, as measured by in-situ ReactIR monitoring of the morpholine carbonyl stretching band at 1,732 cm⁻¹. Manufacturers using continuous-flow microreactor configurations (PFA tubing, ID 1.0 mm, residence time 12 min) suppress the morpholine impurity to <0.05 area%, compared to 1.2–1.8 area% in batch mode.The penultimate intermediate is converted to nemonoxacin malate by salt formation with L-malic acid in water/acetone, a step during which the (3R,4R)-4-hydroxypyrrolidine moiety dictates the crystal form. When the 4-hydroxyl epimerises beyond 0.5% (detected by chiral HPLC on Chiralpak AD-H), the product precipitates as a metastable polymorph designated Form A*, which exhibits a melt-recrystallization exotherm at 189°C (DSC heating rate 10 K/min) and reduced aqueous solubility by 32% at pH 1.2. The compendial specification per the Chinese Pharmacopoeia 2020 for nemonoxacin malate limits total related substances to ≤1.0% and the (3S,4S) diastereomer to ≤0.3%. Only the thermodynamically stable polymorph (Form B) is incorporated into capsule and injection formulations; its dissolution profile must meet the Q≥80% criterion in 30 minutes using USP Apparatus II at 50 rpm in 900 mL of 0.1 N HCl.Transient thermal excursions during solvent exchange for the chiral building block — specifically, when methyl tert-butyl ether is distilled from the Boc-protected compound at jacket temperatures exceeding 45°C — generate trace quantities of the dehydro-pyrrolidine derivative through R-elimination of water. This impurity, once carried into the naphthyridone coupling step, acts as a chromophoric quencher that reduces photostability assay recovery under ICH Q1B (Option 2) by 8–15%. Multi-tonne campaigns therefore mandate thin-film evaporators with residence times below 90 seconds during solvent stripping.

Asymmetric Hydrogenation Ligand Assembly from the Pyrrolidine Scaffold

A structurally orthogonal application domain converts the same Boc-protected amino alcohol into bidentate P,N-ligands for iridium- and rhodium-catalysed enantioselective hydrogenation of prochiral enamides and α,β-unsaturated esters. The primary derivatisation sequence involves mesylation of the C-4 hydroxyl (methanesulfonyl chloride, Et₃N, DCM, 0°C) followed by nucleophilic displacement with diphenylphosphine in the presence of potassium tert-butoxide. The resulting phosphino-pyrrolidine ligand, after Boc cleavage, coordinates to [Ir(COD)Cl]₂ in THF to generate a precatalyst that delivers enantiomeric excesses of 94–97% for the reduction of methyl (Z)-2-acetamido-3-phenylacrylate at 25 bar H₂ and substrate-to-catalyst ratios up to 5,000:1. The free ligand loading in the formulation step is maintained at 1.2 mol% with respect to the metal precursor, providing the optimal balance between turnover frequency and catalyst lifetime before deactivation by phosphine oxide formation.From a quality assurance perspective, the ligand intermediate is tested for optical rotation (specification [α]D²⁵ = +18.5° ± 1.0°, c = 1.0, CHCl₃) and diastereomeric purity by ¹⁹F NMR of the corresponding Mosher’s ester derivative (≥99.0% de). Residual phosphine oxide content, detectable by ³¹P NMR at δ 29.3 ppm, must not exceed 0.5 area% because it functions as a competitive inhibitor in the catalyst activation cycle. The ultimate products are custom-synthesised enantiomerically pure amino acid derivatives, chiral alcohols for pharmaceutical intermediates, and fragrance ingredients that require rigorous demonstration of stereochemical integrity under ISO 9001:2015 certified development workflows.

Peptidomimetic Turn Inducers and the Enantiomeric Purity Specification Threshold

The constrained pyrrolidine ring system bearing a Boc-protected amine and a free hydroxyl group at the 3- and 4-positions provides a conformational lock that mimics the i+1 and i+2 residues of a type II’ β-turn when incorporated into linear peptides. Medicinal chemistry groups utilise this compound as a proline surrogate in the solid-phase synthesis of peptidomimetic inhibitors targeting serine proteases and aspartyl proteases. The building block is coupled onto chlorotrityl resin-bound peptide chains using HATU and DIPEA in DMF at a 3.0-fold molar excess relative to the resin loading, with a double-coupling protocol (2 × 45 minutes) applied whenever the N-terminal residue prior to the pyrrolidine is sterically hindered (e.g., β-branched amino acids). Incomplete incorporation, recognisable by a positive Kaiser test after the standard capping step with acetic anhydride/pyridine, mandates a third coupling cycle.At the DSP stage, the crude cleaved peptide is analysed by LC-MS; the pyrrolidine-modified peptide must exhibit a single peak with the expected molecular ion and no detectable deletion sequence (LOD 0.05%). The chiral purity of the Boc-amino alcohol raw material is the single most critical quality attribute: even 0.3% of the (3S,4S) enantiomer translates to approximately 12% diastereomeric peptidomimetic impurity after resin cleavage because the unnatural configuration places the hydroxyl group in a disfavoured axial orientation that accelerates diketopiperazine-mediated chain termination. Incoming material is therefore released only after passing a chiral GC assay (Chirasil-Dex CB column, 25 m × 0.25 mm, oven program 150°C to 200°C at 2°C/min) with an enantiomeric excess guarantee of ≥99.5%. The downstream deliverables are lead-optimisation-stage peptide-based inhibitors and constrained cyclic peptide libraries employed in cell-based target engagement screening campaigns operating under ICH E6(R3) Good Clinical Practice expectations for downstream data integrity.

Comparative Regulatory and Processing Thresholds Across the Dominant Downstream Sectors
Sector	Addition Ratio (mol/mol substrate)	Critical Process Impurity	Specification Limit	Primary Reference Standard
Moxifloxacin API coupling	1.05–1.12	8-Ethoxy analogue (trans-etherification)	≤0.10%	Ph. Eur. 2254
Nemonoxacin malate	1.15–1.25 (total, incl. 8–12% scavenged)	Fused morpholine by-product	≤0.15%	ChP 2020 (nemonoxacin malate)
Asymmetric hydrogenation ligand	1.2 mol% vs metal precursor	Phosphine oxide (δ 29.3, ³¹P NMR)	≤0.5 area%	ISO 9001:2015 (process)
Solid-phase peptidomimetic assembly	3.0-fold excess over resin loading	Deletion sequence (resin-bound)	LOD 0.05%	Chiral GC ≥99.5% ee

What Occurs When the Boc Deprotection pH Transgresses 3.8 in Pilot-Plant Batches?

A recurring failure mode observed during scale-up of the deprotection step common to all the above applications involves uncontrolled pH drift during the quench of HCl salts. The Boc-pyrrolidine amino alcohol is converted to its hydrochloride salt in an organic medium, after which aqueous neutralisation with NaOH to pH 7.0–7.5 liberates the free amino alcohol for extraction. If the local pH within the aqueous layer transiently exceeds 3.8 before full mixing is achieved — a scenario frequently encountered in 500-litre reactors using bottom-mounted Rushton turbines at agitation rates below 80 rpm — the tertiary amine undergoes rapid N-carboxylation with dissolved CO₂, generating a carbamate species that partitions into the organic phase. Carbamate carry-over into the subsequent amidation or nucleophilic displacement step causes a yield depression of 15–22% and produces a new impurity that reverts only upon refluxing with 6 N HCl for 6 hours. Effective mitigation relies on subsurface CO₂-sparging to maintain a 5–10 mm Hg partial pressure of carbon dioxide during the neutralisation hold period, or, alternatively, the use of KOAc-buffered quench solutions to limit transient acidity spikes. This operational boundary is documented in numerous process development reports and is routinely incorporated into the Batch Manufacturing Record as a critical control point.

Equipment-Dependent Processing Parameters for Kilogram-to-Metric-Tonne Scale Deprotection
Reactor Scale	Agitation Type	Minimum RPM for pH Homogeneity	Permissible CO₂ Partial Pressure	Carbamate Formation Threshold Time (pH > 3.8)
50 L glass line	Anchor + baffle	120	3–5 mm Hg	< 2 min (no yield impact)
500 L glass line	Rushton disc, D/T 0.33	80–90	5–10 mm Hg	8–12 min (15–22% yield loss)
2,000 L Hastelloy	Lightnin A310 + HE-3	65	8–12 mm Hg	< 4 min (with inline static mixer recirculation)

Without a contextual header, the following application segment describes a reductive amination pathway that transforms the Boc-amino alcohol into a family of N-substituted pyrrolidine catalysts used for the kinetic resolution of racemic secondary alcohols. A single-vessel sequence treats the starting material with Dess-Martin periodinane in dichloromethane at 20–25°C to generate the 3-amino-4-oxopyrrolidine intermediate, which is immediately reacted with (R)- or (S)-α-methylbenzylamine and NaBH(OAc)₃ to install a chiral N-benzyl substituent. The diastereomeric products are separated by flash chromatography (hexane/EtOAc 4:1 to 1:1 gradient), affording catalysts with opposite enantioselectivities for benzoyl transfer. When utilised at 5 mol% loading in the acylation of 1-phenylethanol with isobutyric anhydride in toluene/CHCl₃ at –40°C, the resolved alcohol is obtained in 97% ee at 52% conversion (selectivity factor s = 34). The entire sequence is monitored by reaction calorimetry (Mettler RC1); the oxidation step liberates –245 kJ/mol and requires controlled addition of the oxidising agent over 90 minutes to maintain the internal temperature below the decomposition onset of the α-keto pyrrolidine, determined by DSC to be 78°C (exotherm 520 J/g). The terminal products of this process are optically pure benzylic alcohols, chiral building blocks for organocatalytic desymmetrisation, and prostanoid intermediate fragments that must satisfy residual solvent limits under USP <467>.

Chiral Integrity Preserved Across Telescoped Deprotection–Acylation Sequences

Preparation of the free amine on multi-kilogram scale begins with (2R,4R)-4-hydroxyproline. After esterification and tosylation, a Curtius rearrangement using diphenylphosphoryl azide in the presence of benzyl alcohol installs the amine as a Cbz carbamate. Following hydrogenolysis over 5% Pd/C at 40 psi, the crude diastereomeric mixture is subjected to Boc protection with di-tert-butyl dicarbonate (1.2 equiv) in dichloromethane/water using potassium carbonate at 0–5 °C. In a prototype campaign conducted in a 50 L glass-lined reactor, the addition rate was moderated to maintain internal temperature below 8 °C; after 16 h, the organic phase was separated, dried over sodium sulfate, and concentrated. Crystallization from ethyl acetate/heptane (1:3 v/v) afforded the title compound in 68% overall yield from the diamine hydrochloride with diastereomeric purity of 99.7% as measured by HPLC using an Inertsil C18 column (acetonitrile/10 mM ammonium formate buffer pH 3.0). The free amine is susceptible to oxidative discoloration; headspace oxygen control during packaging (<0.5% O₂) and addition of 50 ppm BHT stabiliser extend colour-stability to >18 months under 2–8 °C storage.

When three consecutive transformations are performed in a single vessel—Boc removal, Schotten-Baumann acylation with a 2-fluorophenylacetyl chloride, and re-installation of the Boc group—the competing acylation of the secondary 4-hydroxyl group can consume up to 15% of the electrophile if the amine is not fully liberated first. The optimal protocol involves deprotection with 4 M HCl in dioxane (2.0 equiv relative to substrate) at 10–15 °C for 2 h, followed by solvent switch to dichloromethane and slow addition of 2.2 M aqueous sodium carbonate until the pH of the aqueous phase reaches 8.5. Only after complete neutralisation is the acyl chloride introduced dropwise while maintaining the jacket temperature at 0 °C. Under these conditions, O-acylation is suppressed to <1.0%, allowing the subsequent Boc reprotection with di-tert-butyl dicarbonate in tetrahydrofuran/water to proceed with minimal by-product formation. Process mass intensity for the telescoped sequence was 18.7 kg per kg of isolated product, a figure that underscores the material’s suitability for industrial campaigns where orthogonal protecting group strategies are paramount.

Why Does the (3R,4R) Configuration Outperform Its Enantiomer in DPP-4 Inhibitor Scaffolds?

In a series of triazolopiperazine-based dipeptidyl peptidase‑4 (DPP-4) inhibitors, the (3R,4R) trans-3-amino-4-hydroxypyrrolidine fragment gave a median IC50 of 0.45 nM (fluorogenic Gly-Pro-AMC substrate, 100 mM Tris, pH 7.8, 37 °C), whereas the (3S,4S) enantiomer exhibited an IC50 of 38 nM, representing a 84-fold drop in potency. In silico docking calculations (Glide SP, OPLS4 force field) locate the (3R)-ammonium group in a bidentate salt bridge with Glu205 and Glu206, while the (4R)-hydroxy group donates a hydrogen bond to the backbone carbonyl of Ser209. Inversion of both stereocentres displaces the pyrrolidine ring by 1.8 Å from the S1 pocket floor, preventing occupation of the lipophilic S2 subsite. Importantly, even 2% enantiomeric contamination can shift the observed IC50 in compound libraries by more than 20%, leading to false negative screening hits. The trans relationship is also mandatory for maintaining metabolic stability: rat liver microsome incubations (NADPH regeneration system, 30 min) show >95% of the parent remaining for (3R,4R)-derived analogues, versus <70% for the cis (3R,4S) isomers, which undergo CYP3A4-mediated oxidation at the C-4 alcohol more rapidly.

Quality Control Parameters for the Free Base
Parameter	Specification	Method
Appearance	White to off-white crystalline powder	Visual
Assay (anhydrous, solvent-free basis)	≥ 98.0% w/w	HPLC, USP <621>
Enantiomeric Excess	≥ 99.0%	Chiral HPLC, Chiralpak IA
Water Content	≤ 0.50%	Karl Fischer, USP <921> Method Ia
Melting Range	86–91 °C	USP <741>
Residue on Ignition	≤ 0.10%	USP <281>
Heavy Metals	≤ 10 ppm	USP <231> Method II
Specific Optical Rotation [α]D20	+14.5° to +16.5° (c 1, CHCl₃)	USP <781>

Quality Control Parameters for the Free Base

Parameter

Specification

Method

Appearance

White to off-white crystalline powder

Visual

Assay (anhydrous, solvent-free basis)

≥ 98.0% w/w

HPLC, USP <621>

Enantiomeric Excess

≥ 99.0%

Chiral HPLC, Chiralpak IA

Water Content

≤ 0.50%

Karl Fischer, USP <921> Method Ia

Melting Range

86–91 °C

USP <741>

Residue on Ignition

≤ 0.10%

USP <281>

Heavy Metals

≤ 10 ppm

USP <231> Method II

Specific Optical Rotation [α]D20

+14.5° to +16.5° (c 1, CHCl₃)

USP <781>

Stability Under Simulated GMP Storage Conditions

Forced degradation studies following ICH Q1A(R2) conditions revealed that the solid API is robust. When held at 40 °C/75% RH in an open petri dish for 6 months, the principal degradant DP-1 (retention time 2.3 min relative to parent at 8.1 min) was identified as the Boc-removed 3-amino-4-hydroxypyrrolidine by LC–MS (m/z 103.1 [M+H]+) at a level of 1.2%. A secondary degradant at RRT 1.4, likely the corresponding diketopiperazine dimer, amounted to 0.3%. Under ICH long-term conditions (25 °C/60% RH, double PE bag with silica gel desiccant), no impurity exceeded 0.1% after 12 months. The material is minimally hygroscopic; however, when humidity surpasses 70% RH, water uptake of 0.8% w/w was measured after 48 h. A pre-use drying protocol—vacuum drying at 35 °C and 10 mbar for 4 h—readily restores water content to ≤ 0.20% (Karl Fischer, USP <921>). Residual solvents in commercial GMP lots are controlled to ICH Q3C limits: dichloromethane <60 ppm, ethyl acetate <500 ppm, n-heptane <500 ppm. Analysis is performed by headspace GC using a DB‑624 capillary column (30 m × 0.32 mm, 1.8 µm film), with an oven program from 40 °C (hold 5 min) to 240 °C at 20 °C/min. Palladium from the synthesis is controlled to ≤ 5 ppm by ICP-MS.

When the synthetic route incorporates a palladium-catalyzed hydrogenolysis of a Cbz carbamate prior to Boc introduction, the intermediate (3R,4R)-3-amino-4-hydroxypyrrolidine hydrochloride must be isolated under a carbon dioxide-free atmosphere to prevent formation of the corresponding carbamic acid salt, which precipitates as a poorly soluble crust on the reactor walls. Scrubbing the nitrogen overlay through a 1 M KOH trap and maintaining a slight positive pressure of 0.1 bar eliminated this fouling, enabling a 98% step yield. Moreover, the liberated amine cannot be stored in solution above −10 °C for more than 6 h without measurable oxidation; LC-MS monitoring showed a new peak with m/z 202.2, consistent with nitrone formation. Consequently, the Boc group is reintroduced immediately after filtration and solvent exchange into dichloromethane.

The cis-3,4 diastereomer, (3R,4S)-tert-butyl 3-amino-4-hydroxypyrrolidine-1-carboxylate (CAS 139507-40-2), differs fundamentally in both conformational behaviour and application profile. X‑ray structures reveal that the cis arrangement forces the pyrrolidine ring into a highly strained twist conformation where the amino and hydroxyl groups occupy pseudoequatorial and pseudoaxial positions, respectively. This imparts a 6.2 kcal/mol higher ring‑flip barrier relative to the trans isomer, as determined by dynamic 1H NMR exchange spectroscopy (line‑shape analysis at 500 MHz). In peptide couplings, the cis amine exhibits a 3‑ to 5‑fold slower acylation rate with HATU due to increased steric shielding, often requiring 2.5 equiv of the carboxylic acid to reach full conversion. Moreover, the cis hydroxyl is less prone to oxidation, but the compound displays a 4% rate of epimerisation at the amine centre during long‑term solution storage in DMSO‑d6 over 48 h at 25 °C, attributed to a reversible retro-aza-Michael pathway. Consequently, the trans (3R,4R) isomer remains the preferred choice when both high nucleophilicity and configurational stability are required in multi‑step medicinal chemistry arrays.

If TMS-Diazomethane Esterification Triggers Ring Opening

When the free carboxylic acid of a (3R,4R)‑derived β‑amino acid surrogate—obtained after coupling with a halogenated benzoic acid—was treated with trimethylsilyldiazomethane (2.0 M in hexanes, 1.2 equiv) in methanol/toluene at 0 °C, the methyl ester formed quantitatively within 30 min without affecting the Boc carbamate. However, if the Boc group had been removed beforehand, the resulting primary amine underwent competitive N‑methylation (12% of N‑CH₃ derivative) via a Betti reaction pathway. Therefore, retaining the Boc protection during esterification is critical; this differential reactivity highlights the value of the Boc derivative in synthesis of amino acid building blocks for peptide mimics. Additionally, the presence of the free hydroxyl does not interfere, as esterification is O‑selective only at the carboxy terminus when trans‑4‑OH is not activated.

Comparative Reactivity of Common N-Protecting Group Derivatives on the (3R,4R) Scaffold
Protecting Group	Deprotection Conditions	Half-life in 20% TFA/DCM	Orthogonal Stability	Typical ee After Deprotection	Scalability Note
Boc	4 M HCl/dioxane or 20% TFA/DCM	<5 min	Stable to Pd/C hydrogenolysis	>99%	Well-suited for batch reactors; no heavy metal scavenging needed
Cbz	H₂, 5% Pd/C, 40 psi	>24 h	Labile to hydrogenolysis; stable to TFA	97%	Epimerisation risk at elevated pressure; moderate scale
Fmoc	20% piperidine in DMF	>24 h	Base-labile; stable to acids	99%	Dibenzofulvene scavenging complicates work-up; not preferred for scale
Alloc	Pd(PPh₃)₄ (cat.) + PhSiH₃	>24 h	Stable to TFA and piperidine	96%	Tin and palladium impurities increase purification cost at scale

Comparative Reactivity of Common N-Protecting Group Derivatives on the (3R,4R) Scaffold

Protecting Group

Deprotection Conditions

Half-life in 20% TFA/DCM

Orthogonal Stability

Typical ee After Deprotection

Scalability Note

Boc

4 M HCl/dioxane or 20% TFA/DCM

<5 min

Stable to Pd/C hydrogenolysis

>99%

Well-suited for batch reactors; no heavy metal scavenging needed

Cbz

H₂, 5% Pd/C, 40 psi

>24 h

Labile to hydrogenolysis; stable to TFA

97%

Epimerisation risk at elevated pressure; moderate scale

Fmoc

20% piperidine in DMF

>24 h

Base-labile; stable to acids

99%

Dibenzofulvene scavenging complicates work-up; not preferred for scale

Alloc

Pd(PPh₃)₄ (cat.) + PhSiH₃

>24 h

Stable to TFA and piperidine

96%

Tin and palladium impurities increase purification cost at scale

In a pilot campaign directed at a DP2 receptor antagonist, the Boc-protected trans-amino alcohol was coupled to a 5-chlorothiophene-2-carboxylic acid derivative using HATU (1.05 equiv) and DIEA (2.2 equiv) in DMF at 0–5 °C. Chiral HPLC analysis of the crude amide after aqueous workup (Chiralcel OD-H, hexane/isopropanol 85:15) revealed <0.3% of the epimer derived from racemisation at the amine α‑carbon. The 4-hydroxy group remained intact for subsequent selective silylation with TBDMSCl/imidazole in DMF, which proceeded in 94% isolated yield. Throughout the coupling, strict anhydrous conditions were maintained: Karl Fischer titration of the reaction solvent showed water content <50 ppm, achieved by pre-treatment with activated 4Å molecular sieves. A single deviation where water rose to 250 ppm led to premature Boc deprotection (7% of the deprotected amine), causing a di‑acylation impurity that required additional flash chromatography purification. Thus, the operational reliability of this building block critically depends on rigorously dried solvents and inert atmosphere during acid‑sensitive manipulations, a constraint well‑documented in process development reports.

HS Code	681080
Chemical Formula	C10H20N2O3
Molecular Weight	216.28
Appearance	Solid (usually white or off - white)
Physical State At Room Temp	Solid
Melting Point	Data needed
Boiling Point	Data needed
Solubility In Water	Limited solubility
Solubility In Organic Solvents	Soluble in some polar organic solvents
Pka Value	Data needed
Chirality	Chiral, (3R,4R) configuration
Stereochemistry	Specific (3R,4R) stereochemistry
Functional Groups	Amino, Hydroxy, Carboxylate, Pyrrolidine ring, tert - Butyl group

Packing	100g of (3R,4R)-Tert - Butyl 3 - Amino - 4 - Hydroxypyrrolidine - 1 - Carboxylate in sealed vial.
Shipping	(3R,4R)-Tert - Butyl 3 - Amino - 4 - Hydroxypyrrolidine - 1 - Carboxylate is shipped in accordance with chemical transportation regulations. It's carefully packaged to prevent breakage and ensure safety during transit, often via specialized carriers.
Storage	(3R,4R)-Tert - Butyl 3 - Amino - 4 - Hydroxypyrrolidine - 1 - Carboxylate should be stored in a cool, dry place away from direct sunlight. Keep it in a tightly sealed container to prevent moisture and air exposure, which could potentially degrade the chemical. Store it in an area separate from incompatible substances to avoid any chemical reactions.

(3R,4R)-Tert-Butyl 3-Amino-4-Hydroxypyrrolidine-1-Carboxylate

Moxifloxacin Side-Chain Condensation — A Thermally Sensitive Amide Coupling Workflow

Why Does the C-4 Hydroxyl Configuration Destabilise Nemonoxacin Polymorph A?

Asymmetric Hydrogenation Ligand Assembly from the Pyrrolidine Scaffold

Peptidomimetic Turn Inducers and the Enantiomeric Purity Specification Threshold

What Occurs When the Boc Deprotection pH Transgresses 3.8 in Pilot-Plant Batches?

Get Free Quote of Bouling Chemical Co., Limited

Chiral Integrity Preserved Across Telescoped Deprotection–Acylation Sequences

Why Does the (3R,4R) Configuration Outperform Its Enantiomer in DPP-4 Inhibitor Scaffolds?

Stability Under Simulated GMP Storage Conditions

If TMS-Diazomethane Esterification Triggers Ring Opening