反应详情

To a solution of 2-bromo-6-chloromethylpyridine (2.14 g, 10.4 mmol) obtained in Step 1 of Example 1 in ethanol (30 ml), 2-methyl-2-(1-thiocarbamoylpiperidin-4-yl)propionic acid ethyl ester (2.44 g, 9.43 mmol) obtained in Step 1 was added and the mixture was heated at reflux for 5 hours. The reaction solution was cooled to room temperature, dimethylformamide dimethylacetal (1.9 ml, 14 mmol) and triethylamine (3.9 ml, 28 mmol) were added, and heated at reflux for 1 hour. After the reaction solution was concentrated, water was added, and the solution was extracted with ethyl acetate and washed with a saturated brine. The organic layer was dried over magnesium sulfate and the residue obtained by vacuum concentration was purified by chromatography on silica gel (n-hexane:ethyl acetate=2:1 to 1:1) and the title compound (2.48 g, 60%) was obtained.

1. temperaturethe mixture was heated
2. temperatureat reflux for 5 hours
3. temperatureheated
4. temperatureat reflux for 1 hour
5. concentrationAfter the reaction solution was concentrated
6. additionwater was added
7. extractionthe solution was extracted with ethyl acetate
8. washwashed with a saturated brine
9. dry with materialThe organic layer was dried over magnesium sulfate
10. customthe residue obtained by vacuum concentration
11. customwas purified by chromatography on silica gel (n-hexane:ethyl acetate=2:1 to 1:1)