Sodium Hydroxide → HCID 178488041, compound

Participants

Reaction Steps

A 3L 3-necked flask equipped with a mechanical stirrer was charged with methyl 2-{4-[(5-methoxy-2-{[(4-methoxy-3,5-dimethyl(2-pyridyl))methyl]sulfonyl}benzimidazolyl)sulfonyl]phenoxy}acetate (Intermediate A27, 13.75 g, 0.024 mol) in glyme (1200 mL). To this vigorously stirring solution was added 0.1 N NaOH solution (300 mL). The resulting mixture was concentrated under reduced pressure at 47° C. The residue was triturated with fresh ethyl acetate (100 mL) for a total of four times. The residue was placed under high vacuum for 1 hr to give 17 g of a gummy solid. In a 1L 3-necked flask equipped with a mechanical stirrer was placed 16 g of this solid (equivalent to 13.3 g sodium salt, 0.0226 mol) in water (250 mL). The solution was washed by stirring with ethyl acetate (250 mL) for 1 hr and then the layers were separated. HPLC analysis of the ethyl acetate layer showed 64% omeprazole and 33% unreacted sulfoxide methyl ester. A fresh 250 mL of ethyl acetate was added to the aqueous layer. The resulting mixture was stirred and acidified to pH 3-4 with ca. 40 mL of 0.5 N hydrochloric acid. The ethyl acetate layer was separated quickly, because product started to crystallize, and placed in a freezer overnight. The crystals were collected and air dried to give 6.7 g (53%) of the methyl 2-{4-[(5-methoxy-2-{[(4-methoxy-3,5-dimethyl(2-pyridyl))methyl]sulfonyl}benzimidazolyl)sulfonyl]phenoxy}acetate.

Provenance & Evidence