Tributylphosphine → 4-(4-{3-[(2S)-2-methylpyrrolidinyl]propoxy}phenyl)-tetrahydro-2H-pyran-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(4-hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile (203 mg, 1.0 mmol) and tri-n-butylphosphine (299 μL, 1.20 mmol) in toluene (6 mL) were added to a solution of 3-[(2R)-2-methylpyrrolidin-1-yl]propan-1-ol (172 mg, 1.20 mmol) in toluene (6 mL) and tetrahydrofuran (2 mL) at ambient temperature. 1′1-azobis(N,N-dimethylformamide) (206 mg, 1.20 mmol) was added and the reaction heated to 85° C. overnight. The reaction mixture was concentrated in vacuo followed by addition on dichloromethane (30 mL). The organic solution was then washed with NaOH (2.0M, 2×20 mL), dried with Na2SO4 and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 98:2:0.2 to 96:4:0.4 to give the title compound as a pale yellow oil (70 mg, 21%). HRMS (ESI+) 329.2224 (M+H)+.

Provenance & Evidence