Water → Cyclopropyl(3-fluoro-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidin-1-yl)methanone

Participants

Reaction Steps

To a solution of the 3-(4-(3-fluoroazetidin-3-yl)phenyl)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (Preparation 9, 94 mg) in 2 mL CH2Cl2 was added pyridine (0.05 mL) followed by cyclopropane carbonyl chloride (31 mg). The reaction was allowed to stir at room temperature for 1 hour. Water (10 mL) was added. The reaction was diluted with an additional 10 mL of CH2Cl2, stirred for 30 minutes at room temperature then passed through a phase separation tube. The CH2Cl2 layer was collected and condensed. The crude material was adsorbed on silica and chromatographed on a 12 g silica column, eluting with a gradient of 20% EtOAc/hexane to 80% EtOAc/hexane. Fractions containing the desired material were combined and concentrated. Et2O (˜½ mL) was added to the resulting film. Placing the flask on high vac overnight resulted in formation of the product as a white foam (87 mg). 1H NMR (CDCl3) δ ppm 7.76 (d, 2H), 7.67 (s, 2H), 7.58 (d, 2H), 4.8-4.7 (m, 1H), 4.6-4.2 (m, 3H), 4.12 (d, 1H), 3.72 (d, 1H), 1.5-1.4 (m, 1H), 1.08 (m, 2H), 0.86 (m, 2H). LC/MS retention time=3.710 minutes, MS calculated for (C23H17Cl3F4N2O2), 534.03; found 535.0 M+H.

Provenance & Evidence