Hydrochloric Acid → (R)-N-((2S,4R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1,5,5,5-pentafluoro-4-hydroxypentan-2-yl)-2-methylpropane-2-sulfinamide

Temperature

-78 °C

To a solution of (R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (0.12 g, 0.299 mmol) in THF (3 ml) at −78° C. was added (trifluoromethyl)trimethylsilane (0.475 ml, 2.99 mmol) dropwise. After 25 min, tetrabutylammonium fluoride, 1.0m in tetrahydrofuran (0.299 ml, 0.299 mmol) was added. The reaction mixture was stirred at −78° C. for 6 h (warmed up to −20° C.). Aqueous 1N HCl (0.8 mL) was added at −78° C. and the reaction was warmed up to rt, diluted with water, extracted with EtOAc (2×), washed with water, dried over Na2SO4, filtered and concentrated. The crude material was purified by chromatography through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 0% to 30% EtOAc in hexane in 20 min to give (R)-N-((2S,4R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1,5,5,5-pentafluoro-4-hydroxypentan-2-yl)-2-methylpropane-2-sulfinamide (30 mg, 0.064 mmol, 21.29% yield) as white solid. MS m/z=471, 473 M+, Calculated for C14H17BrF6N2O2S: 471.26.

1. temperaturewarmed up to −20° C.)
2. temperaturethe reaction was warmed up to rt
3. extractionextracted with EtOAc (2×)
4. washwashed with water
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude material was purified by chromatography through a Redi-Sep® pre-packed silica gel column (40 g)
9. washeluting with a gradient of 0% to 30% EtOAc in hexane in 20 min

ORD record

ord-c3510a77a164480d8c0e9fd0088b3acb

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2