反应详情

温度

62.5 °C

L-(+)-Tartaric acid (47.74 g, 318 mmol) was suspended in 265 g of isopropyl alcohol and 16.91 g of water. The mixture was heated to 60-65° C. to afford a homogeneous solution. One equivalent of (±)-ethyl nipecotate (50 g, 318 mmol) was added while the temperature was maintained at or below 75° C. The mixture was stirred at 70-75° C. for 20-30 minutes, then cooled to 60° C. over 60 minutes. Seed crystals of (R)-(−)-ethyl nipecotate-L-(+)-tartrate (25 mg, 0.08 mmol) were added and the reaction was cooled to 26-30° C. over three hours. The temperature was maintained at 26-30° C. for 30 minutes until precipitation was complete. The product was isolated (62.0 g, 94.8% de) and washed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g). The crude product was slurried in a mixture of isopropyl alcohol (188 g) and water (12 g) at 73-77° C. After stirring for 10-20 minutes, the suspension was cooled to 26-30° C. Temperatures exceeding 30° C. will result in less yield, while a temperature of less than 25° C. resulted in de<98%. The product was isolated by filtration and washed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g). This afforded the title compound as a white powder in 72% yield, 98.8% de.

1. customto afford a homogeneous solution
2. temperaturewas maintained at or below 75° C
3. temperaturecooled to 60° C. over 60 minutes
4. temperaturethe reaction was cooled to 26-30° C. over three hours
5. temperatureThe temperature was maintained at 26-30° C. for 30 minutes until precipitation
6. customThe product was isolated (62.0 g, 94.8% de)
7. washwashed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g)
8. additionThe crude product was slurried in a mixture of isopropyl alcohol (188 g) and water (12 g) at 73-77° C
9. stirringAfter stirring for 10-20 minutes
10. temperaturethe suspension was cooled to 26-30° C
11. customexceeding 30° C.
12. customwill result
13. customin less yield, while a temperature of less than 25° C.
14. customresulted in de<98%
15. customThe product was isolated by filtration
16. washwashed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g)