Indole-5-carbonitrile → 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile

Temperature

27.5 °C

Aluminium chloride (82.44 g) was added to dichloromethane (350 ml) under stirring at 25-30° C. The resulting mass was cooled to 0-5° C., followed by drop-wise addition of 4-chlorobutyryl chloride (87.5 g) for 30-45 minutes at 0° C. and then stirring for 5 minutes at the same temperature. A solution of 5-cyanoindole (50 g) in dichloromethane (350 ml) was added drop-wise to the resulting mass at 0-5° C. within 1-2 hours, followed by stirring for 30 minutes at the same temperature. The temperature of the reaction mass was gradually increased to 25-30° C., followed by stirring for 12-16 hours at the same temperature. The reaction mass was slowly poured into crushed ice (420 g) with slow stirring, the resulting mixture was cooled to 0-5° C. and then stirred for 1 hour at the same temperature. The separated solid was filtered, washed the material subsequently with dichloromethane (2×85 ml) and water (2×85 ml) and then dried at 25-30° C. to produce a solid material (Dry weight: 93 g). The resulting solid was dissolved in ethyl acetate (4000 ml) at 50-55° C., followed by the addition of activated carbon (5 g) and then stirring the mixture for 5 minutes at the same temperature. The resulting mass was filtered through celite bed and washed the bed with hot ethyl acetate (100 ml). The resulting filtrate was initially cooled to 25-30° C. and further cooled to 0-5° C., followed by stirring the mass for 1 hour at the same temperature. The separated solid was filtered, washed with chilled ethyl acetate (100 ml) and then dried the material at 50-55° C. until constant weight to produce 65 g of 3-(4-chlorobutyryl)-1H-indole-5-carbonitrile (Purity by HPLC: 99.2%; Yield: 74.8%).

1. temperatureThe resulting mass was cooled to 0-5° C.
2. stirringstirring for 5 minutes at the same temperature
3. stirringby stirring for 30 minutes at the same temperature
4. temperatureThe temperature of the reaction mass was gradually increased to 25-30° C.
5. stirringby stirring for 12-16 hours at the same temperature
6. additionThe reaction mass was slowly poured
7. temperaturethe resulting mixture was cooled to 0-5° C.
8. stirringstirred for 1 hour at the same temperature
9. filtrationThe separated solid was filtered
10. washwashed the material subsequently with dichloromethane (2×85 ml) and water (2×85 ml)
11. customdried at 25-30° C.
12. customto produce
13. customa solid material (Dry weight: 93 g)
14. dissolutionThe resulting solid was dissolved in ethyl acetate (4000 ml) at 50-55° C.
15. additionfollowed by the addition of activated carbon (5 g)
16. stirringstirring the mixture for 5 minutes at the same temperature
17. filtrationThe resulting mass was filtered through celite bed
18. washwashed the bed with hot ethyl acetate (100 ml)
19. temperatureThe resulting filtrate was initially cooled to 25-30° C.
20. temperaturefurther cooled to 0-5° C.
21. stirringby stirring the mass for 1 hour at the same temperature
22. filtrationThe separated solid was filtered
23. washwashed with chilled ethyl acetate (100 ml)
24. customdried the material at 50-55° C. until constant weight

ORD record

ord-a9d4bbb98e32426b9d3bf13d951a19d7

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09399630B2