Sodium Azide → (2S,3R)-3-Azido-2-(3-chloro-2-fluoro-benzylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1527338Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10](OS(C)(=O)=O)[C@H:9]1[C:18](=[O:29])[NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=1[F:28])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:30]=[N+:31]=[N-:32].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([N:30]=[N+:31]=[N-:32])[C@H:9]1[C:18](=[O:29])[NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=1[F:28])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of (2S,3S)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-3-methanesulfonyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester (1.60 g, 2.35 mmol) and NaN3 (0.370 g, 5.67 mmol) in dry DMF (12 mL) was stirred at 110° C. for 60 h. The mixture was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (3×), the combined organics were washed with brine, dried (phase separator) and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:4 to 1:2) to afford the title compound as a colorless foam. MS (LC-MS): 398 [M+H]+, 342 [MH−tBu]+, 298 [MH−Boc]+; tR (HPLC conditions c): 5.15 min.

Workup

customThe mixture was partitioned between water and EtOAc
extractionThe aqueous layer was extracted with EtOAc (3×)
washthe combined organics were washed with brine
customdried (phase separator)
concentrationconcentrated in vacuo
customThe crude product was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:4 to 1:2)

Sources & evidence

ORD record: ord-b4b1350a52084c1a8a031076112972a0
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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