A mixture of pyrmetazole (0.112 mole) and potassium bicarbonate (0.145 mole) in 100 mL of water and approximately 250 mL of a 4:1; toluene: ethanol mixture was cooled to -5° to -9° C. with stirring. A solution of MMPP (0.67 mol) in 170 mL of water was added dropwise over a 2 hour period. After the MMPP solution was completely added a solution of sodium sulfite (2.2g) in 10 mL of water was added and the mixture was stirred for 15 minutes. The reaction mixture temperature was allowed to warm to 0° C. during this period. The slurry was then diluted with 200 mL of water and 50 mL of methanol and the pH of the slurry was adjusted to 9.1 by addition of 50% aqueous sodium hydroxide. The slurry was aged at 0° to 5° C. for 1 hour and then was filtered. The solid was washed with 50 mL of water and 40 mL cold methanol. Drying of the solid provided 31.3 g of crude omeprazole (81% yield).
