(Trifluoromethyl)trimethylsilane → HCID 86732236, compound

Participants

Reaction Steps

To a cooled (−78° C.) solution of (R)-N-(2-(2,3-difluorophenyl)-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (13.5 g, 44.5 mmol) in THF (300 mL) was added (trifluoromethyl)trimethylsilane (70.7 mL, 445 mmol) via syringe in 5 min (internal temperature was up to −55° C.). After stirring for 20 min, tetrabutylammonium fluoride, 1.0M solution in THF (66.8 mL, 66.8 mmol) was added dropwise via additional funnel (internal temperature −78 to −50° C. during addition). Addition was completed in 20 min. The reaction was stirred at the same temperature for 1 h. LCMS showed the diastereomer ratio was about 2:3 with the major one as the desired product. The reaction was quenched with 1N HCl (45 ml), and then the cool bath was removed. The reaction mixture was allowed to warm to ambient temperature during which water (100 ml) was added. The solution was extracted with EtOAc (2×). The organic extracts were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and the residue was triturated with minimum DCM. The resulted suspension was filtered. The filter cake was rinsed a few times with DCM and dried in air to afford 6.3 g of desired product as an white solid. The filtrate was concentrated and purified by silica gel column (0-70% EtOA/hexane) to afford additional 911 mg of desired product. MS m/z=374.1 [M+H]+. Calculated for C15H20F5NO2S: 373.4

Provenance & Evidence