84348-38-9

Basic information

• Product Name: (S)-4-METHYLENE-PYRROLIDINE-1,2-DICARBOXYLIC ACID 1-TERT-BUTYL ESTER
• Synonyms: 1,2-Pyrrolidinedicarboxylicacid, 4-Methylene-, 1-(1,1-diMethylethyl) ester, (2S)-;(S)-1-(tert-butoxycarbonyl)-4-Methylenepyrrolidine-2-carboxylic acid;N-tert-Butoxycarbonyl-4-methylene-L-proline;N-Boc-4-methylene-L-proline 97%;N-T-BOC-4-METHYLENE-L-PROLINE;(S)-4-METHYLENE-PYRROLIDINE-1,2-DICARBOXYLIC ACID 1-TERT-BUTYL ESTER;BOC-4-METHYLENE-L-PROLINE;N-Boc-4-methylene-L-proline
• CAS NO: 84348-38-9
• Molecular Formula: C₁₁H₁₇NO₄
• Molecular Weight: 227.26
• Product Categories: Heterocycles;pharmacetical
• Mol File: 84348-38-9.mol
• Article Data: 14

Chemical Properties

• Melting Point: 110-114°C
• Boiling Point: 349.859 °C at 760 mmHg
• Flash Point: 165.389 °C
• Appearance: /
• Density: 1.18±0.1 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.513
• Storage Temp.: 2-8°C(protect from light)
• PKA: 3.80±0.20(Predicted)
• Water Solubility: Insoluble in water.
• CAS DataBase Reference: (S)-4-METHYLENE-PYRROLIDINE-1,2-DICARBOXYLIC ACID 1-TERT-BUTYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-4-METHYLENE-PYRROLIDINE-1,2-DICARBOXYLIC ACID 1-TERT-BUTYL ESTER(84348-38-9)
• EPA Substance Registry System: (S)-4-METHYLENE-PYRROLIDINE-1,2-DICARBOXYLIC ACID 1-TERT-BUTYL ESTER(84348-38-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 84348-38-9(Hazardous Substances Data)

Usage

Uses

As important intermediates in various areas such as peptide synthesis, asymmetric synthesis, medicinal chemistry, and polymer chemistry. The fluorous prolins were synthesized from commercially available N-Boc-4-methylene- L-proline.

InChI:InChI=1/C11H17NO4/c1-7-5-8(9(13)14)12(6-7)10(15)16-11(2,3)4/h8H,1,5-6H2,2-4H3,(H,13,14)/t8-/m0/s1

Upstream product

• 163190-46-3 tert-Butyl (2S)-N-tert-butoxycarbonyl-4-methylideneprolinate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1779-49-3 Methyltriphenylphosphonium bromide 
• 84348-37-8 N-tert-butoxycarbonyl-4-oxo-L-proline 
• 144423-03-0 N-phenylsulphonyl-N-propargyl-O-tetrahydropyranyl-(S)-serine benzylester 
• 144422-80-0 N-phenylsulphonyl-N-propargyl-3-bromo-(S)-alanine benzylester 
• 144422-81-1 N-phenylsulphonyl-4-exomethylene-(S)-proline benzylester 
• 84348-39-0 (S)-1-tert-butyl 2-methyl 4-methylenepyrrolidine-1,2-dicarboxylate 
• 20309-87-9 (2S)-4-methylenepyrrolidine-2-carboxylic acid 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 27200-84-6 methyl triphenylphosphonium bromide 

Downstream Products

• 144422-82-2 N-Boc-4-exomethylene-(S)-prolinyl dibenzyl-(S)-aspartate 
• 928063-88-1 C₂₂H₃₀N₂O₅ 
• 928063-63-2 C₂₃H₃₀N₂O₆ 
• 1256388-51-8 methyl [(2S)-1-{(6S)-6-[5-(9,9-difluoro-7-{2-[(1R,3S,4S)-2-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-2-azabicyclo[2.2.1]-hept-3-yl]-1H-benzimidazol-6-yl}-9H-fluoren-2-yl)-1H-imidazol-2-yl]-5-azaspiro[2.4]hept-5-yl}-3-methyl-1-oxobutan-2-yl]carbamate 

Relevant articles and documents

An enantioselective approach to 4-substituted proline scaffolds: Synthesis of (s)-5-(tert-butoxy carbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid

A catalytic and enantioselective preparation of the (S)-4-methyleneproline scaffold is described. The key reaction is a one-pot double allylic alkylation of an imine analogue of glycine in the presence of a chinchonidine-derived catalyst under phase transfer conditions. These 4-methylene substituted proline derivatives are versatile starting materials often used in medicinal chemistry. In particular, we have transformed tert-butyl (S)-4-methyleneprolinate (12) into the N-Boc-protected 5-azaspiro[2.4]heptane-6-carboxylic acid (1), a key element in the industrial synthesis of antiviral ledipasvir.

Ledipasvir preparation method

The invention discloses a Ledipasvir preparation method. The Ledipasvir preparation method includes steps: (1) Ledipasvir intermediate product 1-LD-B preparation; (2) Ledipasvir intermediate product 2-LD-E preparation; (3) Ledipasvir intermediate product 3-LD-F preparation; (4) Ledipasvir intermediate product 4-LD-J preparation; (5) Ledipasvir intermediate product 5-LD-L preparation; (6) Ledipasvir-LD-Q preparation. The Ledipasvir preparation method has advantages of technical maturity and stability, product quality stability, safety and reliability in production process and suitableness for industrial production.

DIHYDROPYRIMIDINE COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS

Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer,