Water → 2-(4-(2,2-Dimethyl-1,3-dioxan-5-yl)methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl-1H-benzimidazole

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Reaction Conditions

Reaction Steps

A toluene (dehydrated)(2.22 ml)-water (2.3 μl, 0.128 mmol) solution of the 2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzimidazole (444 mg, 1.07 mmol) separately obtained in the same manner as described in the steps (11a) to (11g) of Example 11 and D-(−)-diethyl tartrate (80.6 μl, 0.471 mmol) was stirred at 50° C. for 10 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (63.2 μl, 0.214 mmol) was added and the resultant mixture was stirred for further one hour in the same conditions. After the mixture was cooled to room temperature and N,N-diisopropylethylamine (59.6 μl, 0.342 mmol) was added, the resultant mixture was cooled to 0° C. After cumene hydroperoxide (611 μl, 3.31 mmol as the content was regarded as 80%) was added dropwise for 5 minutes at 0° C. to 2° C., the mixture was stirred at 0° C. to 7° C. for 3 hours and 35 minutes in an nitrogen atmosphere. After a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 20 g, elution solvent: dichloromethane, dichloromethane/methanol=20/1). The fractions containing the title compound were collected with ethyl acetate and concentrated to obtain the title compound (388 mg, yield: 84.4%) as a colorless foam.

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