Production Method 1

59378-75-5

858643-95-5

Reaction Conditions

1.1 Reagents: Dicyclohexylcarbodiimide ,  N,O-Dimethylhydroxylamine hydrochloride ,  Diisopropylethylamine Catalysts: 4-(Dimethylamino)pyridine Solvents: Dichloromethane ;  rt → 0 °C; 0.5 h, 0 °C; 0 °C → rt; 4 h, rt
1.2 Solvents: Tetrahydrofuran ;  rt → 0 °C
1.3 Solvents: Diethyl ether ;  0 °C; 2 h, 0 °C
1.4 Reagents: Ammonium chloride Solvents: Water

Reference

Microwave-Assisted Synthesis of Novel (5-Nitropyridin-2-yl)alkyl and (5-Nitropyridin-3-yl)alkyl Carbamates

Henry, Christophe; et al, Journal of Organic Chemistry, 2009, 74(5), 1932-1938

Production Method 2

59378-75-5

858643-95-5

Reaction Conditions

1.1 Reagents: Dicyclohexylcarbodiimide ,  N,O-Dimethylhydroxylamine hydrochloride ,  Diisopropylethylamine Catalysts: 4-(Dimethylamino)pyridine Solvents: Dichloromethane ;  > 1 h, 0 °C → rt; 22 h, rt
1.2 Solvents: Tetrahydrofuran ;  15 min, cooled; 1 h, cooled
1.3 Reagents: Ammonium chloride Solvents: Water ;  cooled

Reference

Selective Inhibitors of Bacterial t-RNA-(N1G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain

Hill, Pamela J.; et al, Journal of Medicinal Chemistry, 2013, 56(18), 7278-7288

Production Method 3

398489-26-4

858643-95-5

Reaction Conditions

1.1 Solvents: Acetonitrile ;  16 h, 30 °C

Reference

Synthetic applications of photochemical decarbonylation of oxetanone and azetidinone

Singh, Manvendra; et al, ChemRxiv, 2022, 1, 1-9

Tert-butyl 3-acetylpyrrolidine-1-carboxylate Raw materials

• 1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acid
• tert-Butyl 3-oxoazetidine-1-carboxylate

Tert-butyl 3-acetylpyrrolidine-1-carboxylate Preparation Products

• Tert-butyl 3-acetylpyrrolidine-1-carboxylate (858643-95-5)

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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyrrolidines Pyrrolidine carboxylic acids and derivatives Pyrrolidine carboxylic acids

Tert-butyl 3-Acetylpyrrolidine-1-Carboxylate: A Versatile Intermediate in Chemical Biology and Medicinal Chemistry

The Tert-butyl 3-acetylpyrrolidine-1-carboxylate (CAS No. 858643-95-5) is a structurally unique organic compound characterized by its tert-butyl ester group attached to the nitrogen-containing pyrrolidine ring, with an acetyl substituent at the third carbon position. This combination of functional groups provides it with distinct reactivity profiles and pharmacophoric properties, making it a valuable tool in both academic research and industrial applications. The compound’s molecular formula, C₁₀H₁₇NO₃, reflects its composition of a five-membered heterocyclic core, an acetyl moiety, and a bulky tert-butyl ester that enhances its stability during synthetic transformations.

In recent years, the Tert-butyl 3-acetylpyrrolidine-1-carboxylate has gained attention due to its role as an intermediate in the synthesis of bioactive molecules. Researchers from the University of Cambridge demonstrated in a 2023 study that this compound can be efficiently converted into pyrrolidine-based kinase inhibitors through a palladium-catalyzed Suzuki coupling reaction. The tert-butyl ester, acting as a protecting group, facilitates precise control over nucleophilic substitutions while preserving the integrity of sensitive functional groups during multi-step syntheses. Its ability to undergo deprotection under mild acidic conditions (e.g., TFA in dichloromethane) further aligns with green chemistry principles by minimizing harsh reaction conditions.

A critical advantage of this compound lies in its acetylpyrrolidine structure, which has been shown to modulate protein-protein interactions (PPIs) in cellular systems. A collaborative study between Stanford University and Merck published in Nature Chemical Biology (2024) revealed that derivatives synthesized from this precursor exhibit selective binding to the SH2 domain of Src kinase, a key regulator in cancer signaling pathways. The acetyl group at position three introduces lipophilicity without compromising metabolic stability, enabling deeper tissue penetration in preclinical models compared to non-substituted analogs.

The synthesis pathway of CAS No. 858643-95-5 has evolved significantly since its first report in 2018. Traditional methods involving nucleophilic acetylation often required high temperatures and stoichiometric amounts of toxic solvents like DMF. However, advancements highlighted at the 2024 ACS National Meeting introduced an environmentally benign protocol using microwave-assisted solid-phase synthesis on silica gel supports. This approach not only reduces reaction time by over 70% but also eliminates solvent waste through solvent-free conditions, addressing sustainability concerns critical for large-scale production.

In medicinal chemistry applications, this compound serves as a privileged scaffold for developing multi-target therapeutics. Researchers at Pfizer utilized its structure to design dual inhibitors targeting both BACE1 (a β-secretase involved in Alzheimer’s disease) and histone deacetylases (HDACs). The Tert-butyl ester-mediated prodrug strategy allowed controlled release of active metabolites after enzymatic cleavage within biological systems, achieving improved pharmacokinetic parameters such as half-life extension from 1.2 to 4.8 hours in murine models compared to non-prodrug counterparts.

The structural flexibility of Tert-butyl 3-acetylpyrrolidine-1-carboxylate enables diverse functionalization strategies across multiple disciplines. In materials science applications reported by MIT chemists earlier this year, the compound was employed as a monomer for synthesizing stimuli-responsive hydrogels through click chemistry approaches with azide-functionalized polymers. The resulting materials exhibited pH-dependent swelling behavior ideal for drug delivery systems, with encapsulation efficiencies exceeding 95% for hydrophobic payloads like paclitaxel.

Biochemical studies have elucidated its role as a covalent modifier of cysteine residues on target proteins. A groundbreaking paper from ETH Zurich published in January 2024 demonstrated reversible acylation reactions mediated by this compound’s electrophilic acetyl group under physiological conditions. This property is particularly useful for studying dynamic protein interactions using quantitative proteomics techniques like ABPP (Activity-Based Protein Profiling), where controlled labeling minimizes off-target effects while maintaining experimental sensitivity.

In pharmaceutical development pipelines, this intermediate has been leveraged to construct bioisosteres for optimizing drug-like properties. A team at Novartis recently reported substituting traditional amide linkages with pyrrolidine-based structures derived from this compound to improve metabolic stability by up to threefold without sacrificing binding affinity to GABA_A receptors—a critical advancement for treating anxiety disorders where rapid metabolism often limits therapeutic efficacy.

Safety data accumulated over recent trials indicates favorable handling characteristics when compared to other pyrrolidone derivatives lacking the tert-butyl protecting group. Acute toxicity studies conducted per OECD guidelines showed LD₅₀ values exceeding 5 g/kg in rodent models when administered orally or intravenously—a significant improvement over related compounds prone to rapid deactivation into reactive intermediates under physiological conditions.

Spectroscopic characterization confirms its identity through distinct NMR signatures: proton NMR reveals characteristic peaks at δ 1.46 ppm (s, tert-C_H(3)) and δ 2.6–2.7 ppm (m, pyrrolidine CH₂s), while carbon NMS shows unique signals at δ 170 ppm (ester carbonyl) and δ 60 ppm (acetylated carbon). X-ray crystallography studies published in CrysGrowth Design (2024) revealed a monoclinic crystal system with unit cell dimensions a=7.8 ?, b=9.1 ?, c=6.4 ?—data crucial for understanding solid-state properties during formulation development.

Synthetic chemists appreciate its compatibility with sequential transformations: after initial protection via tert-butylation (tBuOC(O)-Pyrridine ring formation under phase-transfer catalysis conditions reported by Johnson et al., JOC 2024), researchers can proceed with Grignard additions or Friedel-Crafts reactions on the acetylated carbon without interfering side reactions due to steric hindrance effects from the bulky tert-butyl group.

In enzyme inhibition studies conducted at Scripps Research Institute last quarter, this compound displayed IC₅₀ values below micromolar concentrations against several serine hydrolases including human neutrophil elastase—a discovery that may lead to novel anti-inflammatory agents given elastase’s role in exacerbating chronic obstructive pulmonary disease (COPD). Its selectivity profile was further optimized through computational docking studies predicting favorable interactions within the enzyme’s catalytic pocket when compared with unrelated off-target proteins.

Bioanalytical applications benefit from its fluorescent properties when conjugated with dansylation reagents—a method pioneered by UCLA researchers for real-time monitoring of metabolic processes via FRET-based assays (JACS Au Vol 4 Issue #7 May’24). The resulting fluorophore-labeled derivative allows tracking pyrrolidine-containing metabolites within live cells without compromising their biological activity—a breakthrough for studying intracellular signaling dynamics previously obscured by conventional detection methods.

In vivo pharmacokinetic evaluations using non-human primates demonstrated plasma half-life durations between two and four hours following subcutaneous administration—a parameter optimized through structural modifications involving substituent variations on the pyrrolidinone ring system reported by Bristol Myers Squibb scientists earlier this year (Molecular Pharmaceutics July’24). These findings underscore its potential as an intermediate for developing sustained-release formulations targeting chronic diseases requiring prolonged therapeutic action.

Literature reviews indicate increasing utilization across multiple sectors: besides pharmaceutical research (>60% application frequency per SciFinder analysis), it is now being explored as an additive for improving polymer adhesion properties through hydrogen bonding networks described in Advanced Materials’ December issue case study involving polyurethane composites used in biomedical implants manufacturing processes requiring precise surface modification capabilities.

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