反应详情

温度

2.5 °C

Octanophenone (250 g) and dichloromethane (1250 mL) are charged into a round bottom flask at 25-30° C. and stirred. The mixture is cooled to −10° C. to −5° C. and triethylsilane (327.9 g) is added. A solution of titanium tetrachloride (244.1 g) in dichloromethane (1250 mL) is added over a period of 15 minutes and the obtained reaction mixture is maintained at 0-5° C. for 3 hours. The reaction mixture is filtered through a hyflo bed, washed with dichloromethane (500 mL) and the filtrate obtained is charged into a second round bottom flask. The reaction mass (filtrate) is cooled to −10° C. to −5° C. and aluminium chloride (213.2 g) is slowly added to the reaction mass over a period of 15 minutes. A solution of 3-chloropropionyl chloride (173.5 g) in dichloromethane (500 mL) is added over a period of 15 minutes and the obtained reaction mixture is maintained at −10° C. to −5° C. for 3 hours. Water (2500 mL) precooled to 0-10° C. is slowly added at the same temperature and the reaction mixture is stirred for about 1 hour at a temperature of 25-30° C. The organic layer is separated, washed with 5% sodium bicarbonate solution (1250 mL), followed by 20% brine solution (1250 mL) and the organic layer is concentrated under vacuum at 45° C. to obtain crude product (751 g). The crude product obtained and dimethyl formamide (1500 mL) are charged into a round bottom flask at 25-35° C. and stirred. Sodium nitrite (135.5 g) is added and reaction mixture is maintained at 30-35° C. for 3 hour. Water (2500 mL) and ethyl acetate (2500 mL) are added to the reaction mixture, stirred for 30 minutes. The organic layer is separated and the aqueous layer is extracted with ethyl acetate (500 mL). The organic layers are combined, washed with 5% brine solution (2×2500 mL) and concentrated under reduced pressure at 45° C. Hexane (500 mL) is added to the obtained compound and evaporated under reduced pressure at 45° C. to give the title compound.

1. temperatureThe mixture is cooled to −10° C. to −5° C.
2. customthe obtained reaction mixture
3. filtrationThe reaction mixture is filtered through a hyflo bed
4. washwashed with dichloromethane (500 mL)
5. customthe filtrate obtained
6. additionis charged into a second round bottom flask
7. temperatureThe reaction mass (filtrate) is cooled to −10° C. to −5° C.
8. customthe obtained reaction mixture
9. temperatureis maintained at −10° C. to −5° C. for 3 hours
10. customprecooled to 0-10° C.
11. additionis slowly added at the same temperature
12. stirringthe reaction mixture is stirred for about 1 hour at a temperature of 25-30° C
13. customThe organic layer is separated
14. washwashed with 5% sodium bicarbonate solution (1250 mL)
15. concentrationthe organic layer is concentrated under vacuum at 45° C.
16. customto obtain crude product (751 g)
17. customThe crude product obtained
18. stirringstirred
19. customreaction mixture
20. temperatureis maintained at 30-35° C. for 3 hour
21. stirringstirred for 30 minutes
22. customThe organic layer is separated
23. extractionthe aqueous layer is extracted with ethyl acetate (500 mL)
24. washwashed with 5% brine solution (2×2500 mL)
25. concentrationconcentrated under reduced pressure at 45° C
26. additionHexane (500 mL) is added to the obtained compound
27. customevaporated under reduced pressure at 45° C.