Allyl bromide → Methyl (2S)-2-[(1S)-1-[(tert-butoxycarbonyl)amino]-2-oxo-2-pyrrolidin-1-ylethyl]pent-4-enoate

HRID 2246239Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@H:9]([C:15](=[O:21])[N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[CH2:10][C:11]([O:13][CH3:14])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH2:32](Br)[CH:33]=[CH2:34]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:10]([CH2:34][CH:33]=[CH2:32])[C:11]([O:13][CH3:14])=[O:12])[C:15](=[O:21])[N:16]1[CH2:17][CH2:18][CH2:19][CH2:20]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of the product from Step A (2.05 g, 6.83 mmol) in THF (30 mL) was added potassium hexamethyldisilazide (30.0 mL, 0.5M in toluene, 15.0 mmol) at −78° C. The resulting mixture was stirred at −78° C. for 30 min. Allyl bromide (3.0 mL, 34.7 mmol) was then added. After stirring at −78° C. for 2 h, the reaction was quenched with saturated aqueous ammonium chloride solution. The organic phase was separated and the aqueous phase was extracted with two portions of ethyl acetate. The combined organic layers were washed with brine and concentrated in vacuo. Purification by flash chromatography (30:70 hexanes/ethyl acetate) afforded the desired product (major diastereoisomer from the reaction).

Workup

stirringAfter stirring at −78° C. for 2 h
customthe reaction was quenched with saturated aqueous ammonium chloride solution
customThe organic phase was separated
extractionthe aqueous phase was extracted with two portions of ethyl acetate
washThe combined organic layers were washed with brine
concentrationconcentrated in vacuo
customPurification by flash chromatography (30:70 hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-4fef1507de48408abe928f0731aecc20
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07687492B2

Reaction notes

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