反应详情

温度

120 °C

A microwave vial was charged with methyl 6-bromobenzo[d]isothiazole-3-carboxylate (WO07056582, 85 mg, 0.31 mmol), cesium carbonate (220 mg, 0.68 mmol), tris(dibenzylideneacetone)dipalladium(0) (13 mg, 0.014 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos) (14 mg, 0.028 mmol), and degassed xylene (1.5 mL). The mixture was degassed for 10 minutes and then 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole (I-1H) (115 mg, 0.28 mmol) in xylene (1 mL) was added. The reaction flask was evacuated and backfilled with argon three times and then heated at 120° C. for 12 hours. The reaction mixture was cooled to rt, diluted with ethyl acetate and filtered through a CELITE® pad, the filtrate concentrated, and chromatographed on silica using linear gradient, 20-80%, EtOAc in Hexanes) to give the desired ester as a yellow solid. MS m/z 600.2 (M+1), 622.2. (M+23).

1. customdegassed xylene (1.5 mL)
2. customThe mixture was degassed for 10 minutes
3. customThe reaction flask was evacuated
4. temperatureThe reaction mixture was cooled to rt
5. additiondiluted with ethyl acetate
6. filtrationfiltered through a CELITE® pad
7. concentrationthe filtrate concentrated
8. customchromatographed on silica using linear gradient, 20-80%, EtOAc in Hexanes)