Tetrahydrofuran → HCID 67235388, compound
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@:8]([NH:18][S@@:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20])([CH3:17])[C:9]([F:16])([F:15])C(OCC)=O)[CH:7]=1.[CH3:26][Mg]Br.[O:29]1[CH2:33][CH2:32]CC1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@@:8]([NH:18][S@@:19]([C:21]([CH3:24])([CH3:22])[CH3:23])=[O:20])([C:9]([F:16])([F:15])[C:33]([OH:29])([CH3:32])[CH3:26])[CH3:17])[CH:7]=1Participants
Conditions
- Temperature
- 23 °C
Procedure
A solution of (R)-ethyl 3-(5-bromo-2-fluorophenyl)-3-((R)-1,1-dimethylethylsulfinamido)-2,2-difluorobutanoate (intermediate A3.1) (10.5 g, 23.6 mmol) in anhydrous tetrahydrofuran (150 ml) was cooled to −78° C. and was treated dropwise with a solution of methylmagnesium bromide (3.2 M in 2-methyl-tetrahydrofuran; 59.1 ml, 189 mmol). The cooling bath was removed, and the mixture was stirred at 23° C. for 18 hours. For the workup, the reaction mixture was poured cautiously into a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulphate. Removal of the solvent in vacuum left the (R)-N-((R)-2-(5-bromo-2-fluorophenyl)-3,3-difluoro-4-hydroxy-4-methylpentan-2-yl)-2-methylpropane-2-sulfinamide (10.565 g, 23.6 mmol, 99.7% yield) as a yellow gum, which was used in the next step without further purification. MS (ISP): m/z=430.1 [(M+H)+] and 432.1 [(M+2+H)+].
Workup
- customThe cooling bath was removed
- additionFor the workup, the reaction mixture was poured cautiously into a saturated solution of ammonium chloride
- extractionextracted with ethyl acetate
- washThe organic layer was washed with brine
- dry with materialdried over sodium sulphate
- customRemoval of the solvent in vacuum
Sources & evidence
- ORD record
- ord-f9bbb308531a4177a32afb30f2daf60a
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08785436B2
Reaction notes
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