反应详情

温度

108 °C

Thebaine (500.0 g containing 24.4 wt % water, 378.0 g dry basis, 1.21 mol, 1.0 equiv) is placed in a mixture of 1-methoxy-2-propanol (1304.2 g) and ethanolamine (130.6 g, 2.13 mol, 1.76 equiv) and is heated to 108±2° C. to give almost a complete solution. In another vessel, p-toluenesulfonylhydrazide (PTSH) (480.0 g, 2.57 mol, 2.12 equiv) is dissolved in a mixture of ethanolamine (960.1 g, 15.72 mol, 13.0 equiv) and 1-methoxy-2-propanol (80.1 g) and held at 20-25° C. The PTSH solution is then added slowly to the thebaine mixture at such a rate that the batch temperature remains in the range 108±2° C. and the gas evolution vents safely. After the complete addition, the reaction mixture is allowed to agitate at 108±2° C. and is monitored for reaction completion 0.3 area % thebaine remaining) by in-process HPLC analysis. On completion, the batch is cooled to 15±5° C. Water (1200 g) is then charged to the batch while maintaining the batch temperature at ≦30° C. The resulting slurry is stirred and further cooled to 5±3° C. and held for a minimum of 0.5 to 1 hours. The product is collected by filtration, washed with water (2400 g) and then dried at 55±5° C. to a constant weight to give 8,14-dihydrothebaine (yield, 348.4 g, 91.6% yield; purity, 99.2 area % by HPLC). The process described here in Example 1 is shown schematically in FIG. 1.

1. customto give almost a complete solution
2. customheld at 20-25° C
3. customremains in the range 108±2° C.
4. additionAfter the complete addition
5. temperatureOn completion, the batch is cooled to 15±5° C
6. temperaturewhile maintaining the batch temperature at ≦30° C
7. stirringThe resulting slurry is stirred
8. temperaturefurther cooled to 5±3° C.
9. customheld for a minimum of 0.5 to 1 hours
10. filtrationThe product is collected by filtration
11. washwashed with water (2400 g)
12. customdried at 55±5° C. to a constant weight