Acetone, oxime → (6,7-Difluoro-3-methyl-1,2-benzisoxazol-5-yl)methanol

Participants

Reaction Steps

To a stirred solution of propan-2-one oxime (1.73 g, 23.7 mmol) in THF (25 ml) was added potassium t-butoxide (1M solution in THF, 23.8 mL) at 0° C. under nitrogen atmosphere and the mixture was stirred with warming to room temperature for 1 hour. The mixture was cooled to −78° C. and a solution of 1-(5-((tert-butyldiphenylsilyloxy)methyl)-2,3,4-trifluorophenyl)ethanone (Intermediate 332, 3.0 g, 6.8 mmol) in THF (15 mL) was added to the mixture and stirred for 20 minutes at −78° C. then at −20° C. for 2 hours. The reaction was quenched with a saturated aqueous NH4Cl solution and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, and concentrated to give material that was used for the next step without any further purification. A stirred solution of the material dissolved in ethanol (130 ml) was treated with 5 ml of 5% aqueous HCl at 45° C. for 8 hours. The reaction quenched with 10% aqueous sodium bicarbonate solution and extracted with EtOAc. The organic layer washed with water, dried, and concentrated. The residue was purified over a silica gel flash column (elution with 15-20% EtOAc in hexanes) to give title compound as yellow solid. Yield: 600 mg, (46%).

Provenance & Evidence