Boron tribromide → (+)-6-Fluoro-1-[(1H-indazol-4-yl)amino]-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-2,5-diol

Participants

Reaction Steps

200 mg (0.472 mmol) of the above-described (+)-6-fluoro-5-methoxy-1-[(1H-indazol-4-yl)amino]-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-2-ol is mixed at room temperature with 4.7 ml of a 1 M solution of BBr3 in dichloromethane and stirred for three and one-half hours at room temperature. The reaction mixture is mixed drop by drop with saturated sodium bicarbonate solution at −30° C., specifically until a pH of 8 is reached. After dilution with ethyl acetate, the cold bath is removed, and the batch is stirred vigorously for 15 minutes. After 2× shaking with ethyl acetate, the combined organic extracts are washed with water and saturated brine. After drying on sodium sulfate, and after the solvent is filtered and spun off, the residue is chromatographed on silica gel (mobile solvent dichloromethane/methanol). 171.3 mg (88.6%) of the desired compound is obtained. The angle of rotation, measured at room temperature, is [α]D=+7.3 (c=1, MeOH).

Provenance & Evidence