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
To a solution of (R)-ethyl 3-(5-bromo-2-fluorophenyl)-3-((R)-1,1-dimethylethylsulfinamido)-2,2-difluorobutanoate (intermediate A3.2) (10.5 g, 23.6 mmol) in anhydrous tetrahydrofuran (150 ml) at −78° C. was added dropwise 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 h. Poured cautiously into a saturated solution of ammonium chloride, extracted with ethyl acetate, washed organic layer 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: m/z=430.1 [(M+H)+] and 432.1 [(M+2+H)+].
Workup
- customThe cooling bath was removed
- additionPoured cautiously into a saturated solution of ammonium chloride
- extractionextracted with ethyl acetate
- washwashed organic layer with brine
- dry with materialdried over sodium sulphate
- customRemoval of the solvent in vacuum
Sources & evidence
- ORD record
- ord-85d301568b1348b699fbd5b3ffd7535d
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08877744B2
Reaction notes
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