Potassium Phosphate, Tribasic → Tert-butyl 5-cyclopropyl-2-fluoro-4-((1-(trifluoromethyl)cyclohexyl)methoxy)benzoate

Participants

Reaction Conditions

Reaction Steps

To a mixture of tert-butyl 5-chloro-2-fluoro-4-((1-(trifluoromethyl)cyclohexyl)-methoxy)benzoate (4.37 g, 10.63 mmol), cyclopropylboronic acid (1.37 g, 15.93 mmol), potassium phosphate (10.15 g, 47.81 mmol) and tricyclohexylphosphine tetrafluoroborate (0.39 g, 1.06 mmol) in toluene (60 mL) and water (3 mL) under a nitrogen atmosphere was added palladium acetate (0.12 g, 0.53 mmol). The reaction mixture was heated at 100° C. for 18 hours and then cooled to ambient temperature. Water (20 mL) was added and the mixture, and extracted with ethyl acetate, the combined organic extracts was 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 (3.70 g, 83%): 1H NMR (300 MHz, CDCl3) δ 7.40 (d, J=8.4 Hz, 1H), 6.51 (d, J=12.3 Hz, 1H), 4.07 (s, 2H), 1.99-1.88 (m, 4H), 1.76-1.62 (m, 5H), 1.55 (s, 9H), 1.48-1.24 (m, 2H), 0.91-0.82 (m, 2H), 0.62-0.55 (m, 2H).

Provenance & Evidence