Reaction #59901

Reaction equation

( 10d )

2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole

cumene hydroperoxide

N,N-diisopropylethylamine

sodium hydrogen carbonate

→

title compound

Yield 43.7%

2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole

Yield 43.7%

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   workup.ADDITIONwas added
3. 3
   workup.ADDITIONwas added dropwise in a nitrogen atmosphere
4. 4
   workup.STIRRINGthe mixture was stirred at 0° C. to room temperature for 7 hours
5. 5
   Extractionthe reaction mixture was extracted with ethyl acetate
6. 6
   DryingThe organic layer was dried over sodium sulfate
7. 7
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
8. 8
   OtherThe obtained residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/methanol)

Procedure

To a toluene (dehydrated)(1.5 ml)-water (1.35 μl, 74.8 μmol) solution of 2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole (150 mg, 340 mmol), which was separately obtained in the same manner as described in the steps (10a) to (10d) of Example 10, D-(−)-diethyl tartrate (51.2 μl, 299 μmol) was added and the mixture was stirred at 50° C. for 5 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (44.2 μl, 150 μmol) was added and the resultant mixture was stirred for further one hour. After the mixture was cooled on ice, N,N-diisopropylethylamine (39.1 μl, 224 μmol) was added, and cumene hydroperoxide (188 μl, 1.02 mmol as the content was regarded as 80%) was added dropwise in a nitrogen atmosphere, the mixture was stirred at 0° C. to room temperature for 7 hours. After a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/methanol) to obtain the title compound (68 mg, yield: 43.7%) as a light yellow foam.

Source