Lithium Hexamethyldisilazide → (R)-4-Benzyl-3-[(S)-2-(3,5-dichloro-4'-fluoro-biphenyl-4-ylmethyl)-pent-4-enoyl]-oxazolidin-2-one

HRID 1013832Notes

Reaction equation

[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH2:16][CH:17]=[CH2:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:31][C:32]1[C:37]([Cl:38])=[CH:36][C:35]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)=[CH:34][C:33]=1[Cl:46]>C1COCC1>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@H:15]([CH2:31][C:32]1[C:33]([Cl:46])=[CH:34][C:35]([C:39]2[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=2)=[CH:36][C:37]=1[Cl:38])[CH2:16][CH:17]=[CH2:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

Dissolve (R)-4-Benzyl-3-pent-4-enoyl-oxazolidin-2-one (3.86 mmoles; 1.00 g) in THF (2 mL) and cool the mixture in a dry ice acetone bath. Add Lithium Bis(trimethylsilyl)amide (4.24 mmoles; 4.24 mL) dropwise at −78° C. under nitrogen. Stir the mixture at −78° C. for 10 minutes, and then warm to −25° C. for 1 hour. Cool the mixture back down to −78° C. and add 4-Bromomethyl-3,5-dichloro-4′-fluoro-biphenyl (4.43 mmoles; 1.48 g) in THF (2 mL) dropwise at −78° C. Warm the reaction to ambient temp. After stirring overnight, the LCMS analysis indicated 2 peaks. Purify the mixture over silica gel using hexane to 1:1 EtOAc/hexanes to obtain 1.3 g oil/foam. WY=65.8%, LCMS=89.6% (M+1=512.0).

Workup

temperaturecool the mixture in a dry ice acetone bath
customdropwise at −78° C.
temperaturewarm to −25° C. for 1 hour
temperatureCool the mixture back down to −78° C.
temperatureWarm
customthe reaction to ambient temp
stirringAfter stirring overnight
customPurify the mixture over silica gel

Sources & evidence

ORD record: ord-fae4683314f642bfbea9166a6867edfd
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07981918B2

Reaction notes

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