Ozone → [1-(5-Bromo-2-fluoro-phenyl)-1-difluoromethyl-3-hydroxy-propyl]-carbamic acid tert-butyl ester

HRID 81593Notes

Reaction equation

[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]([C:15]1[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH:12]([F:14])[F:13])[CH2:9][CH:10]=C)([CH3:4])([CH3:3])[CH3:2].C([O-])(O)=[O:25].[Na+].O=[O+][O-].[BH4-].[Na+]>C(Cl)Cl.CO.O=O>[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]([C:15]1[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH:12]([F:14])[F:13])[CH2:9][CH2:10][OH:25])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: -75 °C

Procedure

A suspension of [1-(5-bromo-2-fluoro-phenyl)-1-difluoromethyl-but-3-enyl]-carbamic acid tert-butyl ester (5.11 g, 12.96 mmol) and NaHCO3 (1.63 g, 19.44 mmol) in 90 ml DCM and 30 ml MeOH was cooled to −75° C. A mixture of O3 in oxygen gas was introduced till the blue color persisted. The excess ozone was removed by bubbling through oxygen gas for 10 minutes. NaBH4 (0.981 g, 25.9 mmol) was added as a solid in three portions. The mixture was stirred 10 min at −75° C. and then allowed to warm to 0° C. After 30 min the mixture was poured onto ice-cold 1N HCl and extracted with TBME. The organic phase was washed with 1N HCl, brine, dried with MgSO4.H2O and evaporated. Chromatography on silica gel (hexanes/15-35% EtOAc) provided 4.75 g of the title compound as a colorless resin.

Workup

additionwas introduced till the blue color
customThe excess ozone was removed
customby bubbling through oxygen gas for 10 minutes
temperatureto warm to 0° C
additionAfter 30 min the mixture was poured onto ice-cold 1N HCl
extractionextracted with TBME
washThe organic phase was washed with 1N HCl, brine
dry with materialdried with MgSO4.H2O
customevaporated

Sources & evidence

ORD record: ord-413080e6be824ad99885bd7ae56b8e2b
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846658B2

Reaction notes

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