Potassium Phosphate, Tribasic → HCID 86703746, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 5-chloro-2-fluoro-4-((2-methylcyclohexyl)-methoxy)benzoate (1.50 g, 4.30 mmol), cyclopropylboronic acid (0.55 g, 6.41 mmol), potassium phosphate (3.60 g, 17.2 mmol) and tricyclohexylphosphine tetrafluoroborate (0.31 g, 0.86 mmol) in toluene (15 mL) and water (1.5 mL) under a nitrogen atmosphere was added palladium acetate (0.09 g, 0.43 mmol). The reaction mixture was heated at 130° C. for 30 minutes in the microwave, and then cooled to ambient temperature. Water (20 mL) was added and the mixture extracted with ethyl acetate, 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 tert-butyl 5-cyclopropyl-2-fluoro-4-((2-methylcyclohexyl)-methoxy)benzoate (1.5 g, 4.3 mmol), which was used directly for the next step. To a solution of this compound (1.50 g, 4.30 mmol) in dichloromethane (20 mL) was added trifluoroacetic acid (20 mL). The reaction mixture was stirred at 0° C. for 1 hour and then concentrated in vacuo. The residue was triturated in diethyl ether (10 mL), the solid was filtered, rinsed with diethyl ether (2×10 mL) and dried to give the title compound (0.63 g, 48%): 1H NMR (300 MHz, CDCl3) δ 7.48 (d, J=8.4 Hz, 1H), 6.58 (d, J=12.9 Hz, 1H), 3.87 (dd, J=6.7, 2.3 Hz, 2H), 2.17-1.91 (m, 3H), 1.76-1.31 (m, 8H), 0.98-0.84 (m, 5H), 0.67-0.58 (m, 2H).

Provenance & Evidence