反应详情

温度

2.5 °C

A 1 L, 3-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer, cooling bath, and nitrogen inlet-outlet, was charged with acetyl chloride (205.5 g, 2.62 mole) and cooled to 0-5° C. Aluminum chloride was added in portions (4×36.4 g [145.5 g, 1.09 mole]) at 0-5° C., while maintaining the internal temperature below 15° C. The slurry was cooled to 0-5° C. and stirred for 15 minutes. N-(2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (5×20 g, 0.436 mole) was added in portions over 40 minutes at 10-minute intervals, while maintaining temperature at 0-10° C. The resulting tan solution was stirred at 0-5° C. for 1 hour. To the solution was added 400 mL of heptane, while maintaining the temperature at 0-5° C. The resulting bi-phasic mixture was added to a 0° C. to −5° C. mixture of 1 N HCl (650 mL) and isopropyl acetate (125 mL) in a 5 L, 3-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer, and a cooling bath, while maintaining the internal temperature at 0-25° C. over a period of 20 minutes. The 5 L, round-bottomed flask was rinsed with acetyl chloride (20 mL), followed by heptane (110 mL) and added to the batch. The reaction mixture was warmed to 22-24° C. over a period of 30 minutes and then heated to 40-45° C. and stirred at 40-45° C. for 1 hour. The slurry was cooled to 21-25° C. and stirred for 1 hour. The solids were collected by filtration using a Büchner funnel with suction over a polypropylene filter paper. The filter cake was washed with heptane (2×200 mL) followed by 1 N HCl (350 mL), and deionized water (2×200 mL). The solids were dried at 60-65° C. under vacuum (10-30 torr) with nitrogen bleeding to obtain 106.1 g (yield 90%) of N-(5-acetyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (m.p. 113-115° C.).

1. customA 1 L, 3-necked, round-bottomed flask, equipped with a mechanical stirrer
2. temperaturedigital thermometer, cooling bath, and nitrogen inlet-outlet
3. temperaturewhile maintaining the internal temperature below 15° C
4. temperatureThe slurry was cooled to 0-5° C.
5. temperaturewhile maintaining temperature at 0-10° C
6. stirringThe resulting tan solution was stirred at 0-5° C. for 1 hour
7. temperaturewhile maintaining the temperature at 0-5° C
8. additionThe resulting bi-phasic mixture was added to a 0° C. to −5° C.
9. custom3-necked, round-bottomed flask, equipped with a mechanical stirrer
10. temperaturedigital thermometer, and a cooling bath, while maintaining the internal temperature at 0-25° C. over a period of 20 minutes
11. washThe 5 L, round-bottomed flask was rinsed with acetyl chloride (20 mL)
12. additionadded to the batch
13. temperatureThe reaction mixture was warmed to 22-24° C. over a period of 30 minutes
14. temperatureheated to 40-45° C.
15. stirringstirred at 40-45° C. for 1 hour
16. temperatureThe slurry was cooled to 21-25° C.
17. stirringstirred for 1 hour
18. filtrationThe solids were collected by filtration
19. filtrationfilter paper
20. washThe filter cake was washed with heptane (2×200 mL)
21. customThe solids were dried at 60-65° C. under vacuum (10-30 torr) with nitrogen bleeding