4,6-Dichloropyrimidine → 4-Chloro-6-(2-methoxy-4-nitrophenyl)pyrimidine

Participants

Reaction Conditions

Reaction Steps

2-(2-methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2 g, 7.17 mmol) was dissolved in 20 ml of EtOH and the resulting solution was concentrated to ˜15 ml and diluted with EtOH (30 ml). To this solution was added 4,6-dichloropyrimidine (1.495 g, 10.03 mmol), Bis(triphenylphosphine)palladium(II) chloride (0.075 g, 0.107 mmol) and aqueous potassium hydrogenbicarbonate (2.152 g, 21.50 mmol) (in 10 ml of water) at rt. The resulting mixture was stirred at 80° C. for 2 h. The reaction was concentrated under vacuum. The residue was partitioned between EtOAc/aqueous sodium bicarbonate. The aqueous layer was extracted with EtOAc (3×20 ml). The combined organic layers were washed with aqueous sodium bicarbonate (2×20 ml) and brine (20 ml), dried over magnesium sulfate, filtered and concentrated. The residue was purified via Biotage Horizon system (25 g column of Thomson Single Step, EtOAc/Hexane, Griadient: 0%˜30%) to get 0.66 g (35%) of product as white solid. LC-MS (M+H)+=266.1. 1H NMR (400 MHz, CDCl3) δ ppm 4.07 (s, 3H) 7.90 (d, J=2.26 Hz, 1H) 7.98 (dd, J=8.53, 2.26 Hz, 1H) 8.09 (d, J=1.00 Hz, 1H) 8.26 (d, J=8.53 Hz, 1H) 9.10 (d, J=1.25 Hz, 1H).

Provenance & Evidence