Potassium Phosphate, Tribasic → Tert-butyl 4-((1-cyanocyclohexyl)methoxy)-5-cyclopropyl-2-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

To an argon-degassed solution of tert-butyl 5-chloro-4-((1-cyano-cyclohexyl)methoxy)-2-fluorobenzoate (0.571 g, 1.55 mmol) in toluene (8 mL) and water (1 mL) was added cyclopropylboronic acid (0.66 g, 7.71 mmol), tribasic potassium phosphate (1.02 g, 4.80 mmol), tricyclohexylphosphine tetrafluoroborate (0.28 g, 0.92 mmol), and palladium acetate trimer (0.11 g, 0.47 mmol Pd). The mixture was heated at 150° C. in a microwave reactor for 0.5 hour, then diluted with ethyl acetate (150 mL), washed with a 3:1 mixture of saturated aqueous ammonium chloride and water (2×150 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of ethyl acetate in hexanes from 0-10% to afford the title compound as a yellow syrup (0.50 g, 86%): 1H NMR (300 MHz, CDCl3) δ 7.41 (d, J=8.3 Hz, 1H), 6.46 (d, J=12.2 Hz, 1H), 3.93 (s, 2H), 2.18-2.13 (m, 2H), 2.07-1.98 (m, 1H), 1.82-1.63 (m, 5H), 1.55 (s, 9H), 1.48-1.39 (m, 2H), 1.29-1.21 (m, 1H), 0.94-0.88 (m, 2H), 0.65-0.60 (m, 2H); MS (ES+) m/z 374.0 (M+1).

Provenance & Evidence