反应详情

温度

0 °C

A 250 mL, 4-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer, cooling bath, and nitrogen inlet-outlet, was charged with acetyl chloride (37.68 g, 480 mmol) and cooled to 0±5° C. Aluminum chloride (13.33 g, 100 mmol) was added in 4×3.33 g portions at 0±5° C. while maintaining the temperature below 15° C. The resulting solution was cooled to 0±5° C. and stirred for 5 minutes. N-(5-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (10.29 g, 40 mmol) was added in 5×2.06 g portions over 40 minutes at 10-minute intervals, while maintaining the temperature 0-10° C. The tan solution was stirred at 0±5° C. for an additional 30 minutes. The solution was added to a pre-cooled (0-5° C.) mixture of 1 N HCl (120 mL) and isopropyl acetate (13 mL) in a 500 mL, 3-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer, and a cooling bath, while maintaining the temperature at 0-25° C. over a period of 20 minutes. The 250 mL, round-bottomed flask was rinsed with 3 mL of acetyl chloride followed by 13 mL of heptane and added to the batch. The resulting slurry was warmed to 40-45° C. over a period of 30 minutes and then stirred for additional 1 hour. Heptane (39 mL) was added and the slurry was stirred at 40-45° C. for an additional 15 minutes. The slurry was cooled to 20-25° C. and stirred for 1 hour. The solids were collected by filtration using a Büchner funnel with suction over polypropylene filter paper. The filter cake was washed with 2×10 mL heptane/isopropyl acetate (80:20 v/v), followed by 1 N HCl (36 mL) and deionized water (2×25 mL). The solids were dried at 60-65° C. under vacuum (13-40 mbar, 10-30 torr) with nitrogen bleeding to obtain 11.3 g (94% yield) of N-(5-acetyl-6-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (m.p. 124-127° C.).

1. customA 250 mL, 4-necked, round-bottomed flask, equipped with a mechanical stirrer
2. temperaturedigital thermometer, cooling bath, and nitrogen inlet-outlet
3. temperaturewhile maintaining the temperature below 15° C
4. temperatureThe resulting solution was cooled to 0±5° C.
5. temperaturewhile maintaining the temperature 0-10° C
6. stirringThe tan solution was stirred at 0±5° C. for an additional 30 minutes
7. additionThe solution was added to
8. temperaturea pre-cooled
9. custom3-necked, round-bottomed flask, equipped with a mechanical stirrer
10. temperaturedigital thermometer, and a cooling bath, while maintaining the temperature at 0-25° C. over a period of 20 minutes
11. washThe 250 mL, round-bottomed flask was rinsed with 3 mL of acetyl chloride
12. additionadded to the batch
13. temperatureThe resulting slurry was warmed to 40-45° C. over a period of 30 minutes
14. stirringstirred for additional 1 hour
15. additionHeptane (39 mL) was added
16. stirringthe slurry was stirred at 40-45° C. for an additional 15 minutes
17. temperatureThe slurry was cooled to 20-25° C.
18. stirringstirred for 1 hour
19. filtrationThe solids were collected by filtration
20. filtrationfilter paper
21. washThe filter cake was washed with 2×10 mL heptane/isopropyl acetate (80:20 v/v)
22. customThe solids were dried at 60-65° C. under vacuum (13-40 mbar, 10-30 torr) with nitrogen bleeding