Propionitrile → (2S,4R)-4-(4-Bromo-2-chloro-phenylsulfanyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 69531

반응식

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[C:4]([Cl:9])[CH:3]=1.[CH2:10]([N:12](CC)[CH2:13][CH3:14])[CH3:11].[C:17]([O-:20])([O-:19])=O.[Na+].[Na+].[CH:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].[C:30](#N)CC>>[CH3:30][O:19][C:17]([C@@H:13]1[CH2:14][C@@H:11]([S:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[Cl:9])[CH2:10][N:12]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:20]

참가 물질

반응물 5

HCID 7854Propionitrile

HCID 8471Triethylamine

HCID 10340Sodium Carbonate

HCID 61207tert-Butyl Formate

HCID 199152914-Bromo-2-chlorobenzene-1-thiol

생성물 1

HCID 89736507(2S,4R)-4-(4-Bromo-2-chloro-phenylsulfanyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

실험 절차

CAS #1252633-25-2 (5.3 g, 12.3 mmol, Eq: 1.00) was dissolved in propionitrile (40 ml) and 4-bromo-2-chlorobenzenethiol (3.3 g, 14.8 mmol, Eq: 1.20) was added. Now triethyl amine (2.49 g, 3.43 ml, 24.6 mmol, Eq: 2.00) was added. The reaction mixture was stirred at reflux over night. The reaction mixture was poured into 100 ml 10% Na2CO3 and extracted with EtOAc (2×100 mL). The organic layer was extracted with 100 ml 0.1N HCl, dried over Na2SO4, filtered and evaporated. The crude material was purified by flash chromatography (silica gel, 120 g, 0% to 30% AcOEt in heptane in 30 min) to yield a colorless oil (4.72 g; 85%). m/z=352.1 [M+H-Boc]+.

후처리

temperatureat reflux over night
extractionextracted with EtOAc (2×100 mL)
extractionThe organic layer was extracted with 100 ml 0.1N HCl
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated
customThe crude material was purified by flash chromatography (silica gel, 120 g, 0% to 30% AcOEt in heptane in 30 min)
customto yield a colorless oil (4.72 g; 85%)

출처 및 근거

ORD 기록: ord-3d65d10b676b46029e1ab66c58c20ce0
출처 데이터셋: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
특허 번호: US08822505B2

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