反应详情

To a toluene (10.8 ml) and methanol (1.2 ml) solution of the 2-(((4-(2-(8-ethyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)ethoxy)-3-methylpyridin-2-yl)methyl)thio)-1H-benzimidazole (380 mg, 0.81 mmol) obtained in the step (4h), a toluene (2.7 ml) and methanol (0.3 ml) solution of 3-chloroperbenzoic acid (192 mg, 0.73 mmol as the content was regarded as 65%) was added dropwise at −70 to −60° C. for 10 minutes in a nitrogen atmosphere. The mixture was stirred for one hour in the same conditions. The reaction was terminated by adding a saturated aqueous solution (15 ml) of sodium hydrogen carbonate at the same temperature. The mixture was extracted with chloroform (50 ml) twice and the organic layer was dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (NH silica gel: elusion solvent: ethyl acetate/methanol=1/0-4/1 gradient) and desired fractions were concentrated. The obtained foamy product was re-precipitated with chloroform and diethyl ether and filtered. The operation was repeated four times and the obtained solid was washed with diethyl ether and then dried to obtain the title compound (188 mg, 47.9% yield) as a white solid.

1. additionwas added dropwise at −70 to −60° C. for 10 minutes in a nitrogen atmosphere
2. customThe reaction was terminated
3. additionby adding a saturated aqueous solution (15 ml) of sodium hydrogen carbonate at the same temperature
4. extractionThe mixture was extracted with chloroform (50 ml) twice
5. dry with materialthe organic layer was dried over anhydrous sodium sulfate
6. concentrationconcentrated
7. customThe obtained crude product
8. customwas purified by silica gel column chromatography (NH silica gel: elusion solvent: ethyl acetate/methanol=1/0-4/1 gradient)
9. concentrationdesired fractions were concentrated
10. customThe obtained foamy product was re-precipitated with chloroform and diethyl ether
11. filtrationfiltered
12. washthe obtained solid was washed with diethyl ether
13. customdried