Sodium Chloride → Lansoprazole

Participants

Reaction Steps

2-{[3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylthio}-1H-benzimidazole (1.0 g, 2.83 mmol) was suspended in 8 ml of acetonitrile, followed by the addition of 3.5 ml of a 2N aqueous solution of sodium hydroxide. A solution (2 ml) of N-chlorosuccinimide (453 mg, 3.40 mmol) in N,N-dimethylformamide was added dropwise to the solution at −4° C. to 3° C. The reaction mixture was subsequently reacted at −3° C. to 0° C. for 1.5 hr. To the reaction mixture was added a 10% aqueous solution of sodium thiosulfate (2 ml) was added to the reaction mixture and the resulting mixture was stirred for 2 min, followed by the addition of water (20 ml) and acetic acid (0.4 ml) to adjust the solution to about pH 8.5. Ethyl acetate (20 ml) and sodium chloride (3 g) were added thereto to extract and the aqueous layer was further extracted with ethyl acetate (10 ml). The organic layers were combined, washed with a 15% aqueous solution of sodium chloride (10 ml) for three times, and the solvent was evaporated. Ethyl acetate (3 ml), hexane (7 ml) and toluene (2.5 ml) were added to the resulting oil, and then stirred at room temperature for 1 hr. The resulting crystals were collected by filtration, washed with a solvent mixture (3 ml) of 30% ethyl acetate and hexane for two times, and then dried under reduced pressure, to give the title compound (0.88 g, yield; 84.1%) as grayish white crystals. 1H-NMR (400 MHz, DMSO-d6); δ (ppm) 2.16(s, 3H), 4.74(d,J=13.7 Hz, 1H), 4.87(d,J=13.7 Hz, 1H), 4.88(d,J=8.8 Hz, 1H), 4.91(d,J=8.8 Hz, 1H), 7.08(d,J=5.9 Hz, 1H), 7.29(m, 2H), 7.56(m, 1H), 7.70(m, 1H), 8.27(d,J=5.9 Hz, 1H), 13.55(s, 1H).

Provenance & Evidence