4-(Trifluoromethyl)piperidine hydrochloride → methyl 1-(4-(trifluoromethyl)piperidin-1-ylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 1-(chlorosulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate (250 mg, 0.854 mmol) in DCM (10 mL) at −10° C. was added TEA (0.595 mL, 4.27 mmol) and 4-(trifluoromethyl)piperidine hydrochloride (324 mg, 1.708 mmol). The reaction was allowed to stir for 3 h at −10° C. and slowly warmed to room temperature over 2 h. The reaction was allowed to stir at room temperature for 16 h. The reaction mixture was diluted with DCM (10 mL) and washed with H2O (10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was purified by flash column chromatography using a gradient elution of DCM with 0-25% acetonitrile to provide methyl 1-(4-(trifluoromethyl)piperidin-1-ylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate (280 mg, 0.684 mmol, 80% yield) as a white solid. LCMS (+ESI) m/z=410.1 [M+H]+.

Provenance & Evidence