反应详情

温度

2.5 °C

2-Isopropyl-5-methylaniline (286 g, 1.91 mol) and sodium bicarbonate (270 g, 3.22 mol) were charged in to a round bottomed flask with stirring under nitrogen atmosphere and cooled to 0-5° C. 2-Chloroacetyl chloride (218 g, 1.93 mol) was added drop wise at 0-5° C. over a period of 1 hour. The reaction was stirred at 0-5° C. for 1 hour. After completion of the reaction, purified water (2.86 L) was added and stirred at 25-30° C. for 15 minutes. The layers were then separated. The organic layer was washed with water (2×2.86 L) and with brine (1.43 L). The aqueous layers were combined and extracted with ethyl acetate (1.43 L). The organic layers were dried with sodium sulphate, filtered, and concentrated at 50-55° C. under vacuum (500-600 mm Hg) to 2/5ths volume. Hexanes (2.86 L) were added and the mixture was stirred at 25-30° C. for 1 hour. The solid was filtered, washed with hexanes (1.43 L), and dried at 45-50° C. under vacuum (500-600 mm Hg) to give 2-chloro-N-(2-isopropyl-5-methylphenyl)acetamide as an off-white solid (270 g, 66%): mp 97-99° C.; 1H NMR (300 MHz, CDCl3) δ 8.27 (s, 1H), 7.60 (s, 1H), 7.20 (d, J=7.95 Hz, 1H), 7.04 (d, J=7.89 Hz, 1H), 4.25 (s, 2H), 2.99 (q, J=6.78 Hz, 1H), 2.34 (s, 3H), 1.26 (d, J=6.84 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 164.07, 137.28, 136.33, 132.95, 127.35, 125.62, 124.46, 43.21, 27.86, 22.98, 21.00; ESIMS m/z 226 ([M+H]+).

1. stirringThe reaction was stirred at 0-5° C. for 1 hour
2. customAfter completion of the reaction
3. custompurified water (2.86 L)
4. additionwas added
5. stirringstirred at 25-30° C. for 15 minutes
6. customThe layers were then separated
7. washThe organic layer was washed with water (2×2.86 L) and with brine (1.43 L)
8. extractionextracted with ethyl acetate (1.43 L)
9. dry with materialThe organic layers were dried with sodium sulphate
10. filtrationfiltered
11. concentrationconcentrated at 50-55° C. under vacuum (500-600 mm Hg) to 2/5ths volume
12. additionHexanes (2.86 L) were added
13. stirringthe mixture was stirred at 25-30° C. for 1 hour
14. filtrationThe solid was filtered
15. washwashed with hexanes (1.43 L)
16. customdried at 45-50° C. under vacuum (500-600 mm Hg)