Methanesulfonyl chloride → (2S,3S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-3-methanesulfonyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1527337Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[C:14](=[O:25])[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[F:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][S:27](Cl)(=[O:29])=[O:28]>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][S:27]([CH3:26])(=[O:29])=[O:28])[C@H:9]1[C:14](=[O:25])[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[F:24])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice-cooled solution of (2S,3S)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (0.98 g, 2.64 mmol) in dry pyridine (13 mL) was added methanesulfonyl chloride (0.31 mL, 3.96 mmol). The reaction was stirred at 0° C. for 2 h and then at RT for 72 h. The volatiles were evaporated in vacuo and the residue was partitioned between water and EtOAc. The aqueous layer was repeatedly extracted with EtOAc, the combined organics were washed with 0.1N HCl and brine, dried (phase separator) and concentrated in vacuo to afford the title compound. Brown oil. MS (LC-MS): 451 [M+H]+, 395 [MH−tBu]+, 351 [MH−Boc]+; tR (HPLC conditions c): 5.08 min. The material thus obtained was used without any purification.

Workup

waitat RT for 72 h
customThe volatiles were evaporated in vacuo
customthe residue was partitioned between water and EtOAc
extractionThe aqueous layer was repeatedly extracted with EtOAc
washthe combined organics were washed with 0.1N HCl and brine
customdried (phase separator)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-9c359254899f4e55969c25d87e6739c4
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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