Water → Dexlansoprazole

Participants

Reaction Steps

2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole monohydrate (6 kg, 16.2 mol) was dried in vacuo at 80° C. for 21 hours to give 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole (5.73 kg, water content 0.0364%). 2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole (5.00 kg, 14.1 mol, containing water 1.82 g), toluene (25 L), water (13.18 g, 0.732 mol, as total water content 0.833 mol) and (+)-diethyl tartrate (531 mL, 3.10 mol) were mixed under a nitrogen gas stream. Titanium(IV) isopropoxide (414 mL, 1.40 mol) was added at 50-60° C. under a nitrogen gas stream, and the mixture was stirred at the same temperature for 30 min. Diisopropylethylamine (815 mL, 4.68 mol) was added under a nitrogen gas stream at 15-25° C., and cumene hydroperoxide (7.65 L, content 82%, 42.7 mol) was added at −10° C. to 5° C. and the mixture was stirred at −8° C. to 2° C. for 3 hours to allow reaction.

Provenance & Evidence