1,2-Dimethoxyethane → 4-Methyl-2-(4-trifluoromethylphenyl)pyrimidine

Participants

Reaction Steps

A 20 mL microwave vial was charged with 4-(trifluoromethyl)phenylboronic acid (813 mg, 4.28 mmol), 2-chloro-4-methylpyrimidine (500 mg, 3.89 mmol), bis(triphenylphosphine)palladium(II) chloride (136 mg, 0.194 mmol), and K2CO3 (1075 mg, 7.78 mmol), followed by the addition of DME (9.0 mL), water (3.86 mL) and ethanol (2.57 mL). The mixture was microwaved at 120° C. for 10 minutes. The reaction was repeated for three more batches. To the combined reaction mixtures was added 300 mL EtOAc, washed with 300 mL water and 300 mL brine, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on a Grace Reveleris 80 g column, eluted with 0-40% EtOAc in Hexanes (35 mL/min) to obtain the title compound (3.385 g, 14.21 mmol, 91% yield) as a light yellow solid. MS (ESI+) m/z 239.2 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 8.81 (d, J=5.1, 1H), 8.59 (d, J=8.1, 2H), 7.89 (d, J=8.3, 2H), 7.42 (d, J=5.1, 1H), 2.58 (s, 3H).

Provenance & Evidence