Sodium Chloride → Rabeprazole

Participants

Reaction Steps

2-{[4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methylthio}-1H-benzimidazole (5.0 g 14.6 mmol; referred to as Compound I hereinafter) was dissolved in 20 ml of N,N-dimethylformamide, followed by the addition of a 2N aqueous solution of sodium hydroxide (18 ml). A solution (10 ml) of N-chlorosuccinimide (2.71 g, 20.3 mmol) in N,N-dimethylformamide was added dropwise to the solution at −20° C. to −10° C. The reaction mixture was reacted at −15° C. to −7° C. for 1.5 hr. To the reaction mixture was added a 10% aqueous solution of sodium thiosulfate (5 ml), stirred for 2 min and then, a solution (60 ml) of ammonium acetate (23.1 g) in water was added thereto. 60 ml of ethyl acetate and 10 g of sodium chloride were added thereto to extract the reaction mixture, and the aqueous layer was further extracted with ethyl acetate (40 ml). The organic layers were combined, washed with a 15% aqueous solution of sodium chloride (80 ml) for three times and then, the solvent was evaporated. To the resulting oil was added 12 ml of ethyl acetate, 28 ml of hexane and 10 ml of toluene, followed by stirring at room temperature for 1 hr. The resulting crystals were collected by filtration, washed with a solvent mixture (10 ml) of 30% ethyl acetate and hexane for two times and then, dried under reduced pressure, to give the title compound (4.7 g, yield; 90.6%) as grayish white crystals.

Provenance & Evidence