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

HRID 69531

Reaction equation

HRID 69531 reaction equation
[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]

Participants

6

Reactant 5

HCID 7854PropionitrileHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 61207tert-Butyl FormateHCID 199152914-Bromo-2-chlorobenzene-1-thiol

Product 1

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

Procedure

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]+.

Workup

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

Sources & evidence

ORD record
ord-3d65d10b676b46029e1ab66c58c20ce0
Source dataset
uspto-grants-2014_09
Patent number
US08822505B2

Linked notes

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