Carbon tetrabromide → (3S)-3-(2-Bromoethyl)-4-fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

HRID 1917304Notes

Reaction equation

HRID 1917304 reaction equation
[C:1]([Br:5])(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:25]([O:29][C:30]([C@@:32]1([CH2:47]CO)[CH:36]([F:37])[C:35](=[O:38])[N:34]([C@@H:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH3:40])[CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>ClCCl>[C:25]([O:29][C:30]([C@@:32]1([CH2:47][CH2:1][Br:5])[CH:36]([F:37])[C:35](=[O:38])[N:34]([C@@H:39]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH3:40])[CH2:33]1)=[O:31])([CH3:26])([CH3:27])[CH3:28]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 67490899(3S)-4-Fluoro-3-(2-hydroxyethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 67490900(3S)-3-(2-Bromoethyl)-4-fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl esterYield 110.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Carbon tetrabromide (1.88 g, 5.68 mmol) and triphenylphosphine (1.49 g, 5.68 mmol) were sequentially added to a solution of (3S)-4-fluoro-3-(2-hydroxyethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (1.66 g, 4.74 mmol) in dichloromethane (20 mL) in a nitrogen atmosphere at 0° C. After heating to room temperature, the reaction solution was stirred for one hour and concentrated to about 5 mL. The residue was purified by silica gel column chromatography (dichloromethane→hexane:ethyl acetate=2:1) to give 2.17 g (91%) of the title compound as a white solid.

Workup

  1. concentrationconcentrated to about 5 mL
  2. customThe residue was purified by silica gel column chromatography (dichloromethane→hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-12b30a65bd414a1a9226a614d27c7415
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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