Potassium Phosphate, Tribasic → N-(1-Adamantylmethyl)-2-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-5-chloroisonicotinamide

Participants

Reaction Conditions

Reaction Steps

A solution of 9-borabicyclo[3.3.1]nonane at 0.5 M in tetrthydrofuran (2.78 mL, 1.39 mmol) was added to neat (allyloxy)(tert-butyl)dimethylsilane (0.15 mL, 0.69 mmole). The mixture was heated to 60° C. for 2 hours under nitrogen. The reaction was subsequently cooled to room temperature and a solution of potassium phosphate (0.37 g) in water (1 mL) was added slowly. A solution of N-(1-adamantylmethyl)-2,5-dichloroisonicotinamide (0.20 g, 0.59 mmol; prepared as described in WO 01/94338) in dimethylformamide (3 mL) was added followed by tetrakis(triphenyphosphine)palladium (0) (7 mg). The solution was heated to 70° C. for 2 hours; allowed to cool to room temperature then partitioned between ethyl acetate (20 mL) and brine (10 mL). The aqueous phase was further extracted with ethyl acetate (2×20 mL) and the combined organics were washed with brine (20 mL); dried over magnesium sulphate; filtered and evaporated under vacuum to give the crude product (0.70 g) as a yellow oil, which was used, as such, without any further purification.

Provenance & Evidence