Benzenesulfonyl chloride → (3S)-3-(3-benzenesulfonyloxy-1-propyl)-4-Fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

HRID 1917337Notes

Reaction equation

HRID 1917337 reaction equation
[C:1]([O:5][C:6]([C@@:8]1([CH2:23][CH2:24][CH2:25][OH:26])[CH:12]([F:13])[C:11](=[O:14])[N:10]([C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]1([S:33](Cl)(=[O:35])=[O:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C.O.C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([C@@:8]1([CH2:23][CH2:24][CH2:25][O:26][S:33]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)(=[O:35])=[O:34])[CH:12]([F:13])[C:11](=[O:14])[N:10]([C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 67490810(3S)-4-Fluoro-3-(3-hydroxy-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl esterHCID 86585896Sodium bicarbonate water

Product 1

HCID 86664648(3S)-3-(3-benzenesulfonyloxy-1-propyl)-4-Fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(3S)-4-Fluoro-3-(3-hydroxy-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (12.20 g) was dissolved in dichloromethane (400 mL). Benzenesulfonyl chloride (9.06 mL), triethylamine (10.7 mL), and 4-dimethylaminopyridine (2.04 g) were added under ice-cooling, and the mixture was stirred at room temperature for 12.5 hours. Saturated sodium bicarbonate water was added to the reaction solution, and the mixture was stirred for 30 minutes, followed by extraction with dichloromethane. The organic layer was sequentially washed with a 10% citric acid solution and brine, dried over anhydrous sodium sulfate, and filtered. Thereafter, the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane:ethyl acetate=8:2→1:1) to give 11.7 g of the title compound as a pale yellow oil.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 30 minutes
  3. extractionfollowed by extraction with dichloromethane
  4. washThe organic layer was sequentially washed with a 10% citric acid solution and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThereafter, the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bb9681926861472cbfd6d93ecf7d9a88
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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