反应详情

温度

100 °C

To a solution of tert-butyl 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluorobenzoate (15.80 g, 40.00 mmol), cyclopropylboronic acid (5.16 g, 60.00 mmol) and potassium phosphate (38.20 g, 180.00 mmol) in toluene (160 mL) and water (8 mL) was bubbled with a nitrogen atmosphere for 10 min, tricyclohexylphosphine tetrafluoroborate (1.47 g, 3.99 mmol) and palladium acetate (0.45 g, 2.00 mmol) was added to this reaction mixture. The reaction mixture was heated to 100° C. for 18 h and then cooled to ambient temperature. Water (100 mL) was added and the mixture was extracted with ethyl acetate (100 mL×3), the combined organics were washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) afforded the title compound as a colorless solid (13.8 g, 86%): 1H NMR (300 MHz, CDCl3) δ 7.37 (d, J=8.4 Hz, 1H), 6.47 (d, J=12.9 Hz, 1H), 3.49 (s, 2H), 2.05-1.95 (m, 4H), 1.78-1.61 (m, 12H), 1.55 (s, 9H), 0.91-0.84 (m, 2H), 0.64-0.58 (m, 2H).

1. temperaturecooled to ambient temperature
2. extractionthe mixture was extracted with ethyl acetate (100 mL×3)
3. washthe combined organics were washed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated in vacuo
6. customPurification of the residue by column chromatography (5% ethyl acetate in hexanes)