(Trifluoromethyl)trimethylsilane → HCID 117833456, compound

Participants

Reaction Conditions

Reaction Steps

Intermediates XVII-1 and XVII-2: In a dry flask under an inert atmosphere a solution of (S)—N—((S)-1,1-difluoro-2-(2-fluorophenyl)-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (XVI-1) (1.45 g, 4.51 mmol) in THF (30 ml) was treated at 0° C. with (trifluoromethyl)trimethylsilane (1.28 g, 1.33 ml, 9.02 mmol) and dropwise with TBAF (1 M in THF, dried over molecular sieves 4 Å; 0.451 ml, 0.451 mmol). The slightly exothermic addition was completed within 3 min, thereafter the reaction mixture was stirred at 0° C. for 3 h, then left to warm to r.t. and stirred overnight. For the workup, the reaction mixture was quenched with a saturated solution of NH4Cl and extracted three times with AcOEt. The organic layers were washed with brine, dried over MgSO4 and evaporated at reduced pressure. The crude product was purified by chromatography on silica gel (eluent: heptane/AcOEt; gradient: 0-90% AcOEt) to yield the (S)-2-methyl-N-((2S,4R)-1,1,5,5,5-pentafluoro-2-(2-fluorophenyl)-4-hydroxypentan-2-yl)propane-2-sulfinamide (XVII-1) (yellow oil, 377 mg as an approximately 7:3-mixture with its O-trimethylsilyl derivative) as the faster eluting epimer, the (S)-2-methyl-N-((2S,4S)-1,1,5,5,5-pentafluoro-2-(2-fluorophenyl)-4-hydroxypentan-2-yl)propane-2-sulfinamide (XVII-2) (yellow solid, 209 mg, 12% yield) as the second eluting epimer [MS: m/z=392.5 (M+H)+], and the starting aldehyde (yellow oil, crystallized on standing, 627 mg, 36% yield).

Provenance & Evidence