反应详情

2-Bromo-6-chloromethylpyridine obtained in Step 1 of Example 1 (2.90 g, 14.0 mmol) was dissolved in ethanol (30 ml) and 1-thiocarbamoylpiperidine-4-carboxylic acid ethyl ester (3.00 g, 13.9 mmol) obtained in Step 1 was added, and the mixture was heated to reflux for 2 hours. The reaction solution was cooled to room temperature, dimethylormamide dimethylacetal (2.8 ml, 21.1 mmol) and triethylamine (5.9 ml, 42.3 mmol) were added, and the mixture was heated at reflux for 1 hour. After concentration, water was added and the reaction 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 silica gel chromatography (n-hexane:ethyl acetate=50:50 to 0:100) and the title compound (3.60 g, 65%) was obtained.

1. temperaturethe mixture was heated
2. temperatureto reflux for 2 hours
3. temperaturethe mixture was heated
4. temperatureat reflux for 1 hour
5. concentrationAfter concentration, water
6. additionwas added
7. extractionthe reaction 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 silica gel chromatography (n-hexane:ethyl acetate=50:50 to 0:100)