Oxalyl chloride → t-butyl-(1S)-2-chloro-1-[3,5-difluorobenzyl]-2-oxoethylcarbamate

HRID 1869720Notes

Reaction equation

HRID 1869720 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C([Cl:25])=O>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=1)[C:10]([Cl:25])=[O:11])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 65578Oxalyl chlorideHCID 27790093,5-Difluoro-L-phenylalanine, N-BOC protected

Product 1

HCID 9836718t-butyl-(1S)-2-chloro-1-[3,5-difluorobenzyl]-2-oxoethylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid (I) is dissolved in THF and stirred at 20-25°. Oxalyl chloride (1 equivalent) is added and the mixture stirred for about 15 min to give t-butyl-(1S)-2-chloro-1-[3,5-difluorobenzyl]-2-oxoethylcarbamate (XI). The mixture is cooled to <0° and LiCHICl (greater than 2 equivalents) is added. The mixture is stirred until the reaction is complete. The reaction is quenched with water and the product is extracted into ethyl acetate. The combined organic phases are washed with saline, dried over sodium sulfate and concentrated under reduced pressure to give the title compound.

Workup

  1. stirringthe mixture stirred for about 15 min

Sources & evidence

ORD record
ord-e0bf86e1855940308ece1e3d9cffce2e
Source dataset
uspto-grants-2009_12
Patent number
US07638646B2

Reaction notes

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