反应详情

温度

100 °C

To a mixture of tert-butyl 3-((2-chloro-5-fluoro-4-(methoxycarbonyl)- phenoxy)methyl)-azetidine-1-carboxylate (1.2 g, 3.2 mmol), cyclopropylboronic acid (415 mg, 4.8 mmol), potassium phosphate (2.04 g, 9.6 mmol) and tricyclohexylphosphine tetrafluoroborate (118 mg, 0.32 mmol) in toluene (20 mL) and water (1 mL) under a nitrogen atmosphere was added palladium acetate (36 mg, 0.16 mmol). The reaction mixture was heated to 100° C. for 16 h and then cooled to ambient temperature. The mixture was quenched by water (50 mL) and extracted with ethyl acetate (50 mL×3), the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel column (eluting with petroleum ether/ethyl acetate, from 10/1 to 2/1) to afford target compound (1.0 g, 83%) as a pale yellow solid. LCMS (ESI) m/z: 324.3 [M−56+H]+.

1. temperaturecooled to ambient temperature
2. customThe mixture was quenched by water (50 mL)
3. extractionextracted with ethyl acetate (50 mL×3)
4. washthe combined organic layers were washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting residue was purified by silica gel column (eluting with petroleum ether/ethyl acetate, from 10/1 to 2/1)