Methyl 4-(4-fluorophenyl)pyrimidine-2-carboxylate

Synthesis

General procedure for the synthesis of methyl 4-(4-fluorophenyl)pyrimidine-2-carboxylate from 2-chloro-4-(4-fluorophenyl)-pyrimidine: In a 50 mL pressure vial, a methanol (20 mL) solution of 2-chloro-4-(4-fluorophenyl)pyrimidine (1 g, 4.79 mmol) was mixed with PdCl2 (dppf) (0.070 g, 0.096 mmol) and triethylamine (1.336 mL, 9.59 mmol) were mixed. The mixture was pressurized with carbon monoxide (60 psi) and the reaction was stirred at 100 °C for 15 hours. Upon completion of the reaction, the mixture was partitioned between 300 mL of ethyl acetate and 300 mL of water, the organic phase was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was separated by chromatography on a Grace Reveleris 40 g silica gel column, using a hexane solution of 0-100% ethyl acetate (flow rate 30 mL/min) as eluent, to afford the title compound, methyl 4-(4-fluorophenyl)pyrimidine-2-carboxylate (1.428 g, 6.15 mmol, 64.1% yield), as a brown solid.MS (ESI+ ) m/z 233.0 (M + H)+; 1H NMR (300 MHz, DMSO-d6) δ 9.02 (d, J = 5.4 Hz, 1H), 8.34 (dd, J = 9.1, 5.5 Hz, 2H), 8.29 (d, J = 5.4 Hz, 1H), 7.43 (t, J = 8.9 Hz, 2H), 3.95 (s, 3H).

References

[1] Patent: US2012/245124, 2012, A1. Location in patent: Page/Page column 39-40