Diethyl chlorophosphate → 6-Ethynyl-8-trimethylsilanylethynyl-2,2,4,4-tetramethyl chroman

Participants

Reaction Conditions

Reaction Steps

A solution of 6-acetyl-8-trimethylsilanylethynyl-2,2,4,4-tetramethyl chroman (Compound 36, 0.616 g, 1.88 mmol) in anhydrous tetrahydrofuran (3 mL) was cannulated into a stirred, cooled (−78° C.) solution of lithium diisopropyl amide [2.82 mmol in 2 mL of tetrahydrofuran generated from N,N-diisopropyl amine (0.4 mL, 2.82 mmol) and 1.6M solution of n-butyl lithium in hexanes (1.88 mL, 3 mmol)] and the resulting reaction mixture was stirred at the same temperature for 50 min. Diethyl chlorophosphate (0.35 mL, 2.44 mol) was then added and the reaction mixture was allowed to warm to 0° C. over 1.5 h. The reaction mixture was then cannulated into a stirred, cooled (−78° C.) solution of lithium diisopropyl amide [8.46 mmol in 3 mL of tetrahydrofuran generated from N,N-diisopropyl amine (1.2 mL, 8.46 mmol) and 1.6M solution of n-butyl lithium in hexanes (5.64 mL, 9 mmol)]. The reaction mixture was allowed to warm to −30° C. over 2 h. It was then quenched with water and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue that was subjected to flash column chromatography over silica gel (230-400 mesh) using 1-2.5% ethyl acetate in hexane as the eluent to afford the title compound as a white solid (0.29 g, 50%).

Provenance & Evidence