Water → 3-(3,3-Difluoroazetidine-1-carbonyl)-6,7-difluorobenzo[d]isoxazole-5-carbaldehyde

Participants

Reaction Steps

(3,3-Difluoroazetidin-1-yl)(5-(dimethoxymethyl)-6,7-difluorobenzo[d]isoxazol-3-yl)methanone (Intermediate 228, 3.336 g, 9.58 mmol) was dissolved in a 4:1 THF:water mixture (62.5 ml) and heated at 75° C. with tosic acid monohydrate (0.911 g, 4.79 mmol) for three hours. The reaction was allowed to cool to room temperature, diluted with ethyl acetate, washed 3× with saturated NaHCO3, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate. Fractions were combined and concentrated to give the title compound (2.66 g, 8.83 mmol).

Provenance & Evidence