反应详情

温度

30 °C

A mixture of (S)-3-methylamino-1-thiophen-2-yl-propan-1-ol (34.2 g, 200 mmol) and ethyl acetate (400 mL) is heated to 30° C., then a mixture of (+)-camphor-10-sulfonic acid (46.4 g, 200 mmol), ethyl acetate (100 mL) and ethanol (100 mL) is added dropwise at 30° C. in 40 minutes. At the end of the addition, the resulting solution is heated to 50° C., stirred for 15 minutes at that temperature, then cooled to 25° C. Once cold, the reaction mixture is concentrated to dryness and ethyl acetate (500 mL) is added to the residue. The resulting mixture is then heated to reflux, kept at that temperature for 15 minutes, then cooled to 25° C. in 30 minutes while seeding the reaction mixture when the temperature reaches about 40° C. Once cold, the resulting suspension is stirred for 30 additional minutes. Afterwards, the precipitate is filtrated, washed with ethyl acetate (2×50 mL) and dried at 40° C. under vacuum (20 mbar) for 15 h affording a white solid (71.5 g, 89%); 1H-NMR (CDCl3, 400 MHz): 7.2 (1H, dm), 7.0 (1H, m), 6.9 (1H, m), 5.21 (1H, t), 3.3 (3H, m), 2.82 (1H, d), 2.75 (3H, s), 2.50 (1H, m, symm.), 2.3 (3H, m), 2.1 (1H, m), 2.0 (1H, m), 1.85 (1H, d), 1.74 (1H, m, symm.), 1.4 (1H, m), 1.04 (3H, s), 0.82 (3H, s).

1. additionis added dropwise at 30° C. in 40 minutes
2. additionAt the end of the addition
3. temperaturethe resulting solution is heated to 50° C.
4. temperaturecooled to 25° C
5. concentrationOnce cold, the reaction mixture is concentrated to dryness and ethyl acetate (500 mL)
6. additionis added to the residue
7. temperatureThe resulting mixture is then heated
8. temperatureto reflux
9. waitkept at that temperature for 15 minutes
10. temperaturecooled to 25° C. in 30 minutes
11. customreaches about 40° C
12. stirringOnce cold, the resulting suspension is stirred for 30 additional minutes
13. filtrationAfterwards, the precipitate is filtrated
14. washwashed with ethyl acetate (2×50 mL)
15. customdried at 40° C. under vacuum (20 mbar) for 15 h