Reaction #59903

Reaction equation

water

2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzimidazole

( 11g )

2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzimidazole

N,N-diisopropylethylamine

sodium hydrogen carbonate

cumene hydroperoxide

→

title compound

Yield 81.1%

2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole

Yield 81.1%

Solvents

toluene

Conditions

Workup

1. 1
   TemperatureAfter the mixture was cooled to room temperature
2. 2
   workup.ADDITIONwas added dropwise for 10 minutes at 0° C. to 1° C.
3. 3
   workup.STIRRINGthe mixture was stirred for 3 hours and 10 minutes in the same conditions
4. 4
   Extractionthe mixture was extracted with ethyl acetate
5. 5
   DryingThe organic layer was dried over anhydrous sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   OtherThe residue was purified by silica gel column chromatography (NH silica gel: 20 g, elution solvent: dichloromethane, dichloromethane/methanol=20/1)
9. 9
   workup.ADDITIONThe fractions containing the title compound
10. 10
    Otherwere collected with ethyl acetate
11. 11
    Concentrationconcentrated

Procedure

A toluene (dehydrated)(2.96 ml)-water (3.09 μl, 0.172 mmol) solution of the 2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzimidazole (591 mg, 1.43 mmol) separately obtained in the same manner as described in the steps (11a) to (11g) of Example 11 and L-(+)-diethyl tartrate (108 μl, 0.629 mmol) was stirred at 50° C. for 5 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (84.4 μl, 0.286 mmol) was added and the resultant mixture was stirred for one hour in the same conditions. After the mixture was cooled to room temperature and N,N-diisopropylethylamine (79.7 μl, 0.458 mmol) was added, the resultant mixture was cooled to 0° C. After cumene hydroperoxide (816 μl, 4.42 mmol as the content was regarded as 80%) was added dropwise for 10 minutes at 0° C. to 1° C., the mixture was stirred for 3 hours and 10 minutes in the same conditions. 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 (498 mg, yield: 81.1%) as a colorless foam.

Source