Chlorodifluoromethane → N-Boc-(R)-2-(5-bromo-2-difluoromethoxy-benzyl)-morpholine

Participants

Reaction Conditions

Reaction Steps

To a solution of sodium hydroxide (186 mg, 4.64 mmol) in water (1.0 mL) was added tetra n-butylammonium bromide (50 mg, 0.155 mmol) followed by N-Boc-(R)-2-(5-bromo-2-hydroxybenzyl)morpholine (576 mg, 1.55 mmol), example 1, intermediate (a) in dioxane (8.0 mL). The reaction mixture was cooled to 10° C. and chlorodifluoromethane gas passed into the reaction mixture whilst the vessel was stoppered. After 15 mins, the solution was warmed to 23° C. whilst continuing to pass the gas into the solution. After 30 mins, the gas flow was ceased and the reaction stirred for 17 hrs before concentration and partition of the residue between ethyl acetate and water. The crude product was purified by silica gel chromatography, eluting with 10% ethyl acetate/iso-hexane, affording N-Boc-(R)-2-(5-bromo-2-difluoromethoxy-benzyl)-morpholine as an oil (357 mg, 55%).

Provenance & Evidence