2,6-Lutidine → 1-((4S,5R)-5-(4-(6-(aminomethyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-3-yl)-2,2-difluoroethanone

Participants

Reaction Steps

To a solution of tert-butyl (5-(4-((4S,5R)-3-(2,2-difluoroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methylcarbamate (970 mg, 4.5 mmol) in CH2Cl2 (25 mL) at 0° C. is added 2,6-lutidine (460 μL, 3.9 mmol) followed by t-butyldimethylsilyltrifluoromethanesulfonate (700 μL, 2.9 mmol). The reaction is stirred at room temperature for 18 hours. Additional lutidine (230 μL, 1.9 mmol) and t-butyldimethylsilyltrifluoromethanesulfonate (350 μL, 1.4 mmol) is added and contents heated to 35° C. for 1 hour. Saturated NH4Cl is added and the reaction is stirred for 15 minutes. Contents are diluted with CH2Cl2 and separated. The organic phase is washed with saturated NH4Cl, saturated NaHCO3, brine, dried (Na2SO4) and concentrated under vacuum. Crude silyl carbamate is dissolved in tetrahydrofuran (20 mL) and tetrabutylammonium fluoride (0.6 mL, 2.0 mmol) is added and stirred for 20 minutes. Saturated NH4Cl is added and contents are extracted with ethylacetate. The organic phase is washed successively with saturated sodium hydrogen carbonate, brine, dried with Na2SO4 and concentrated under vacuum to afford the title compound (123 mg): m/z (CI) M+H 394.

Provenance & Evidence