Sodium Hydroxide → Pantoprazole

Participants

Reaction Conditions

Reaction Steps

A flask equipped with a stirrer is charged with ethyl acetate (140 ml). Under mixing, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl) methyl]thio]-1H-benzimidazole VI (5 g, 13.6 mmol) is added to the flask followed by 18.8% aq. NaOH (11.5 ml, d=1.16 g ml−1, 4.9 eq.). The reactor is cooled to −10° C. 9.7% NaOCl (9.7 ml, d=1.16 g ml−1, 1.04 eq.) is added dropwise over 15 min. The two-phase mixture is stirred at room temperature for 3 h. The phases are then separated, and 27% aq. sodium metabisulfite (Na2S2O5) (7 ml) is added to the aqueous phase to quench unreacted oxidant. The organic phase is washed with water, and the aqueous phase is washed twice with ethyl acetate. The organic phases are combined, dried over sodium sulfate (Na2SO4), and evaporated under 20 mm Hg vacuum. The resulting oil is triturated with methyl t-butyl ether and filtered to obtain pantoprazole (3.7 g, yield 71%) which contains 0.04% sulfone and 0.03% compound VI as within the limit of UV detection.

Provenance & Evidence