反应详情

温度

-70 °C

The 3-bromo-i-propoxybenzene (200 g, 0.08703 mol) was combined with THF (540 ml) under nitrogen and cooled to about -75° C. n-Butyl lithium (565 ml, 0.8306 mol) was added dropwise while maintaining the mixture at less than -70° C. After 2 hours 1,3-Dimethyl-4-piperidone (106.7 g, 0.8389 mol) was added while maintaining the temperature of the mixture between -80° C. and -70° C. After stirring 2 hours at -70° C., the reaction mixture was then added to 6N HCl (280 ml) while maintaining the temperature at 20°-25° C. The pH was adjusted to 1 with 12 N HCl. The aqueous layer containing product was separated and heptane (320 ml) was added along with 50% NaOH (48 ml, pH=13-14) and the resulting mixture allowed to stand overnight. The mixture was heated to 45° -50° C. and the upper layer was separated. The remaining aqueous layer was extracted with heptane (320 ml) at 45°-50° C. The combined organic fractions were washed with de-ionized water (120 ml) at 45°-50° C. The resulting organic layer was vacuum distilled at a pot temperature of about 55° C. at 100 mmHg. Crystallization from heptane and drying provided 151.8 g of 3-(3-i-propoxyphenyl)-1,3-dimethyl-4-hydroxypiperidine. Melting point 75.0°-76.0° C.

1. additionwas added dropwise
2. temperaturewhile maintaining the mixture at less than -70° C
3. temperaturewhile maintaining the temperature of the mixture between -80° C. and -70° C
4. temperaturewhile maintaining the temperature at 20°-25° C
5. additionThe aqueous layer containing product
6. customwas separated
7. additionheptane (320 ml) was added along with 50% NaOH (48 ml, pH=13-14)
8. waitto stand overnight
9. temperatureThe mixture was heated to 45° -50° C.
10. customthe upper layer was separated
11. extractionThe remaining aqueous layer was extracted with heptane (320 ml) at 45°-50° C
12. washThe combined organic fractions were washed with de-ionized water (120 ml) at 45°-50° C
13. distillationdistilled at a pot temperature of about 55° C. at 100 mmHg
14. customCrystallization from heptane
15. customdrying