反应详情

Cis 1-benzo[1,3]dioxol-5-yl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester hydrochloride of Step 2 (50 g) was dissolved in dichloromethane and 5% aqueous sodium bicarbonate (500 mL). The organic layer was separated and washed with deionized water (500 mL). The organic layer was added into deionized water (50 mL) and treated with sodium bicarbonate (15 g) at 25° C. to 30° C. To the resultant mixture, chloroacetyl chloride (25 g) in dichloromethane (50 mL) was added at a rate sufficient to maintain the temperature of the reaction mixture between 0° C. and 5° C. The reaction mixture was stirred for three hours. After the completion of reaction, dichloromethane (500 mL) and DI water (1 L) were added. The organic layer was separated and washed sequentially with water followed by aqueous sodium bicarbonate solution until the pH was 6.5-7.0, and finally with water. The organic layer was concentrated under reduced pressure to obtain a solid. The solid was dissolved in acetone (750 mL) and the resultant solution was concentrated to a residual volume of about 75 mL. To the concentrated solution, deionized water was slowly added at 20° C. to 25° C. and the resultant mixture was cooled to 0° C. to 5° C. with continuous stirring for 0.5 hours. The solid so obtained was filtered and dried to afford cis 1-benzo[1,3]dioxol-5-yl-2-(2-chloro-acetyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester.

1. customThe organic layer was separated
2. washwashed with deionized water (500 mL)
3. additionThe organic layer was added into deionized water (50 mL)
4. additiontreated with sodium bicarbonate (15 g) at 25° C. to 30° C
5. additionTo the resultant mixture, chloroacetyl chloride (25 g) in dichloromethane (50 mL) was added at a rate sufficient
6. temperatureto maintain the temperature of the reaction mixture between 0° C. and 5° C
7. customAfter the completion of reaction, dichloromethane (500 mL) and DI water (1 L)
8. additionwere added
9. customThe organic layer was separated
10. washwashed sequentially with water
11. concentrationThe organic layer was concentrated under reduced pressure
12. customto obtain a solid
13. concentrationthe resultant solution was concentrated to a residual volume of about 75 mL
14. additionwas slowly added at 20° C. to 25° C.
15. temperaturethe resultant mixture was cooled to 0° C. to 5° C.
16. stirringwith continuous stirring for 0.5 hours
17. customThe solid so obtained
18. filtrationwas filtered
19. customdried