Methyl 3-(benzyloxy)-1-(2,3-dihydroxypropyl)-4-oxo-1,4-dihydropyridine-2-carboxylate

1206102-06-8

77-78-1

1206102-07-9

GENERAL STEPS: 3-(Benzyloxy)-1-(2,3-dihydroxypropyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid (4.302 kg, 13.47 mol) was added to the reactor, followed by sodium bicarbonate (1.69 kg, 20.09 mol) and deionized water (242 g). N-methylpyrrolidone (21.4 kg) was added to the mixture, stirred and warmed up to 28-35 °C. Dimethyl sulfate (2.34 kg, 18.30 mol) was added slowly and dropwise through the addition funnel over a period of 1-3 h. The reaction temperature was maintained at 28-33°C. Stirring of the reaction mixture was continued at this temperature for 14 hours. Upon completion of the reaction, the mixture was cooled to below 5 °C and neutralized with aqueous hydrochloric acid (561 mL of concentrated hydrochloric acid dissolved in 2806 g of deionized water) to pH 6. A pre-cooled 20% brine solution (consisting of 8.7 kg of sodium chloride, 20 kg of deionized water, and 14.8 kg of ice) was slowly added to the reaction vessel to a controlled temperature of no more than 100 °C. The reaction was carried out at a temperature of 0-100 °C. The reaction temperature was controlled at 0-100 °C. The mixture was stirred at 0-100°C for 2.5 hours. After completion of the reaction, the slurry was vacuum filtered and the filter cake was washed twice with deionized water (15 kg). The wet solid product was dried under vacuum at 45-55 °C to constant weight to afford the target product, methyl 3-(benzyloxy)-1-(2,3-dihydroxypropyl)-4-oxo-1,4-dihydropyridine-2-carboxylate, as a light yellow solid (3.77 kg, 84% yield, 99.42% HPLC purity).1H NMR (300 MHz, DMSO-d6) δ 7.60 (d, J = 7.5 Hz, 1H), 7.36 (m, 5H), 6.28 (d, J = 7.5 Hz, 1H), 5.23 (d, J = 5.4 Hz, 1H), 5.10 (ABq, J = 10.8 Hz, 2H), 4.85 (m, 1H), 3.98 (dd, J = 14.3, 2.4 Hz, 1H), 3.79 (s, 3H), 3.70 (dd, J = 14.3, 9.0 Hz, 1H), 3.58 (m, 1H), 3.23 (m, 1H).