Toluene → tert-Butyl 3-cyclopropyl-4-fluorobenzylcarbamate

Participants

Reaction Conditions

Reaction Steps

Under N2, a toluene (4.70 mL)/water (0.235 mL) solution of tert-butyl 3-bromo-4-fluorobenzylcarbamate (0.300 g, 0.986 mmol) was treated with potassium phosphate tribasic (0.733 g, 3.45 mmol), cyclopropylboronic acid (0.110 g, 1.282 mmol), and tricyclohexenylphosphene (0.028 g, 0.099 mmol) in was added palladium(II) acetate (0.011 g, 0.049 mmol). The reaction was stirred at 100° C. for 3 h. The solution was diluted with water (15 mL) then extracted with ethyl acetate (2×15 mL). The organic extracts were combined, washed with brine (20 mL), then dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL) to give the title compound as a white crystalline solid (0.230 g, 88% yield). 1H NMR (500 MHz, CDCl3) δ: 6.98-7.05 (1 H, m), 6.90-6.97 (1 H, m), 6.79 (1 H, dd, J=7.02, 1.53 Hz), 4.75 (1 H, brs), 4.21 (2 H, d, J=5.49 Hz), 2.02-2.09 (1 H, m), 1.45 (9 H, s), 0.93-1.01 (2 H, m), 0.66-0.75 (2 H, m).

Provenance & Evidence