4-Bromo-2-fluorobenzotrifluoride → (S)-2-(tert-butyldimethylsilyloxy)-1-(2-fluoro-3-(trifluoromethyl)phenyl)propan-1-one
Reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[C:4]([F:12])[CH:3]=1.C([Li])CCC.[Si:18]([O:25][C@@H:26]([CH3:34])[C:27](N1CCCC1)=[O:28])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C1COCC1>[Si:18]([O:25][C@@H:26]([CH3:34])[C:27]([C:3]1[CH:2]=[CH:7][CH:6]=[C:5]([C:8]([F:11])([F:10])[F:9])[C:4]=1[F:12])=[O:28])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (4.93 g, 20.3 mmol) in THF (50 mL) cooled to −78° C. was added slowly over 10 min butyl lithium (8.11 mL, 20.3 mmol, 2.5 M in hexanes). The reaction was transferred via cannula to a cooled solution (−78° C.) of 110 (4.35 g, 16.9 mmol) in THF (50 mL). The reaction was stirred for 10 min after all aryl lithium was added. The reaction was quenched with H2O and extracted with DCM. The organic layer was concentrated and the resulting residue was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (1 to 5% EtOAc) to afford impure (S)-2-(tert-butyldimethylsilyloxy)-1-(2-fluoro-3-(trifluoromethyl)phenyl)propan-1-one (112) which was used without further purification.
Workup
- additionwas added
- customThe reaction was quenched with H2O
- extractionextracted with DCM
- concentrationThe organic layer was concentrated
- customthe resulting residue was purified by SiO2 chromatography
- washeluting with an EtOAc/hexane gradient (1 to 5% EtOAc)
Sources & evidence
- ORD record
- ord-e2d91b5ef02c48b78a6c9e280e36b83a
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133187B2
Reaction notes
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