Boron tribromide → 5-[3-(4-Hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide

Participants

Reaction Conditions

Reaction Steps

The product of example 106(53 mg, 0.16 mmol) was dissolved in dichloromethane (5 mL) and the solution was cooled to 0° C. Boron tribromide (1M in dichloromethane, 0.52 mL, 0.52 mmol) was added and the solution was stirred at 0° C. for 35 minutes. Further boron tribromide (1M in dichloromethane, 0.52 mL, 0.52 mmol) was added and stirring continued at 0° C. for 30 minutes. The reaction was then quenched with saturated sodium hydrogen carbonate solution (20 mL) and stirred at room temperature for 18 hours. The aqueous layer was separated, extracted with ethyl acetate (25 mL) and the combined organic solution was dried over magnesium sulfate and concentrated in vacuo to give a gum. The gum was re-dissolved in dichloromethane (5 mL) and the solution was cooled to −10° C. Boron tribromide (1M in dichloromethane, 0.52 mL, 0.52 mmol) was added and the mixture was stirred at −10° C. for 1 hour. The reaction was then quenched with saturated sodium hydrogen carbonate solution (20 mL) and the organic layer was separated and extracted with ethyl acetate (20 mL). The combined organic solution was dried over magnesium sulfate, concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with pentane:ethyl acetate/methanol/0.88 ammonia (90/10/1), 75:25 to 50:50, to afford the title compound as a colourless foam in 27% yield (14 mg).

Provenance & Evidence