Ethyl Acetate → (S)-N-((S)-2-(5-bromo-2-fluorophenyl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide

Temperature

23 °C

(S)-methyl 3-(5-bromo-2-fluorophenyl)-3-((S)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate (intermediate E3.1) (1.65 g, 3.83 mmol) was dissolved in tetrahydrofuran (80 ml) and lithium borohydride (668 mg, 30.7 mmol) was added at 5° C. in two portions. The turbid solution was stirred at 23° C. for 16 hours. The reaction mixture was poured into ice water and ethyl acetate was added. Saturated NH4Cl solution (50 ml) was added slowly and the mixture was stirred vigorously for 45 min until the gas evolution finished. The organic layer was separated, dried over Na2SO4, filtered and evaporated to give a yellow oil. The residue was purified by chromatography on 50 g silica gel with ethyl acetate/heptane 0-80% to give (S)—N—((S)-2-(5-bromo-2-fluorophenyl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide (815 mg, 2.03 mmol, 52.8% yield) as a colourless oil. MS (ISN): m/z=399.9 [M−H]− and 401.9 [M+2−H]−.

1. additionwas added
2. stirringthe mixture was stirred vigorously for 45 min until the gas evolution
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customevaporated
7. customto give a yellow oil
8. customThe residue was purified by chromatography on 50 g silica gel with ethyl acetate/heptane 0-80%

ORD record

ord-86e702d1df5a42f9977f5068de58c519

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987255B2