反应详情

To a reactor containing dichloromethane (4 L) was added 4-isopropylamino-1-(4-methoxypyrid-3-ylmethyl)piperidine monobenzoic acid salt (1.5 kg, 3.89 mol) while maintaining the temperature of the mixture at −5° C. to 5° C. The container used to add the salt was rinsed with dichloromethane (1.5 L) and the rinse was added to the reaction mixture. The temperature of the reaction mixture was then adjusted to 0° C. to 5° C. and 7,7-dimethoxyheptanal (790 g, 4.25 mol, 93.8% purity by GC) was added while maintaining the temperature of the reaction mixture between 0° C. to 5° C. The container used to add the 7,7-dimethoxyheptanal was rinsed with dichloromethane (0.8 L) and the rinse was added to the reactor. The resulting reaction mixture was then stirred at 0° C. to 5° C. for 1 hour. Sodium triacetoxyborohydride (1.07 kg, 5.05 mol) was then added in 7 equal portions over a period of 1 hour while maintaining the temperature of the reaction mixture between −5° C. to 5° C. The container used to add the sodium triacetoxyborohydride was rinsed with dichloromethane (0.8 L) and the rinse was added to the reaction mixture. The reaction mixture was then stirred at 0° C. to 5° C. for 21 hours. An aqueous solution of potassium carbonate (500 g) in deionized water (8.6 L) was then added to the reaction mixture while maintaining the temperature of the mixture between to 0° C. to 25° C. The resulting mixture was stirred for 2 hours at a temperature between 15° C. to 25° C. The layers were then allowed to separate over a period of 30 minutes and the organic layer was collected. The washing procedure with aqueous potassium carbonate solution was repeated 2 times. To the organic layer was then added an aqueous solution of sodium chloride (5.7 kg) in deionized water (15 L) while maintaining the temperature between to 15° C. to 25° C. The resulting mixture was stirred for 30 minutes at a temperature between 15° C. to 25° C. and then the layers were allowed to separate over a period of 30 minutes. The organic layer was collected and to this layer was added dichloromethane (1.5 L). The resulting solution containing the title compound was stored under a nitrogen atmosphere, protected from light, at 0° C. to 5° C. until used in the subsequent reaction.

1. temperaturewhile maintaining the temperature of the mixture at −5° C. to 5° C
2. additionto add the salt
3. washwas rinsed with dichloromethane (1.5 L)
4. additionthe rinse was added to the reaction mixture
5. customwas then adjusted to 0° C. to 5° C.
6. temperaturewhile maintaining the temperature of the reaction mixture between 0° C. to 5° C
7. washwas rinsed with dichloromethane (0.8 L)
8. additionthe rinse was added to the reactor
9. customThe resulting reaction mixture
10. temperaturewhile maintaining the temperature of the reaction mixture between −5° C. to 5° C
11. washwas rinsed with dichloromethane (0.8 L)
12. additionthe rinse was added to the reaction mixture
13. stirringThe reaction mixture was then stirred at 0° C. to 5° C. for 21 hours
14. additionAn aqueous solution of potassium carbonate (500 g) in deionized water (8.6 L) was then added to the reaction mixture
15. temperaturewhile maintaining the temperature of the mixture between to 0° C. to 25° C
16. stirringThe resulting mixture was stirred for 2 hours at a temperature between 15° C. to 25° C
17. customto separate over a period of 30 minutes
18. customthe organic layer was collected
19. additionTo the organic layer was then added an aqueous solution of sodium chloride (5.7 kg) in deionized water (15 L)
20. temperaturewhile maintaining the temperature between to 15° C. to 25° C
21. stirringThe resulting mixture was stirred for 30 minutes at a temperature between 15° C. to 25° C.
22. customto separate over a period of 30 minutes
23. customThe organic layer was collected and to this layer
24. additionwas added dichloromethane (1.5 L)
25. additionThe resulting solution containing the title compound
26. customprotected from light, at 0° C. to 5° C.
27. customuntil used in the subsequent reaction