(NE,R)-N-[[4-(1,1-difluoroethyl)-2-fluorophenyl]methylidene]-2-methylpropane-2-sulfinamide → N-((S)-1-(4-(1,1-difluoroethyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

温度

0 °C

To a solution of (R,E)-N-(4-(1,1-difluoroethyl)-2-fluorobenzylidene)-2-methylpropane-2-sulfinamide (497 mg, 1.706 mmol) in DCM (9.59 mL) was added methylmagnesium bromide (3M in diethylether; 1.20 mL) at 0° C. The reaction mixture was allowed to stir for 1 hr at 0° C., gradually allowed to warm to room temperature and stirred for 1 hr at room temperature. The mixture was cooled to 0° C., additional methylmagnesium bromide (3M in diethylether; 0.5 mL) was added and stirring was continued for 30 min at 0° C. The reaction mixture was carefully quenched with saturated aqueous ammonium chloride solution (6 mL) and diluted with water (20 mL). The separated aqueous phase was extracted with DCM (30 mL). The combined organic layers were washed with brine (50 mL), concentrated under reduced pressure. The residue was purified by column chromatography [SiO2, 24 g, heptane/ethyl acetate] providing N—((S)-1-(4-(1,1-difluoroethyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (349 mg) as a white solid. LCMS m/z 308.2 (M+H)+, Rt 0.91 min.

1. temperatureto warm to room temperature
2. stirringstirred for 1 hr at room temperature
3. temperatureThe mixture was cooled to 0° C.
4. stirringstirring
5. waitwas continued for 30 min at 0° C
6. customThe reaction mixture was carefully quenched with saturated aqueous ammonium chloride solution (6 mL)
7. additiondiluted with water (20 mL)
8. extractionThe separated aqueous phase was extracted with DCM (30 mL)
9. washThe combined organic layers were washed with brine (50 mL)
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by column chromatography [SiO2, 24 g, heptane/ethyl acetate]

ORDレコード

ord-062d2ef82e8e494daa403af6ca58626e

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09434719B2