反应详情

Trimethylaluminum (2M in toluene; 3.0 mL, 6.0 mmol) was diluted into 30 mL dichloromethane to which piperidine (0.55 g, 6.5 mmol) and methyl benzo-2,1,3-thiadiazole-5-carboxylate (1.16 g, 6.00 mmol) were added. The reaction was stirred at room temperature for 2 hours and concentrated to one-half the volume by rotary evaporation. Dry toluene (25 mL) was added and the reaction solution was heated to 80° C. for 1 hour. Additional piperidine (about 0.2 g) was added and the temperature was increased to 100° C. for 1 hour. The solution was allowed to cool to room temperature and stirred overnight, at which time it was quenched with 10% citric acid and hydrochloric acid. The solution was diluted with ethyl acetate and sequentially washed with 10% citric acid, saturated sodium hydrogen phosphate and saturated sodium chloride, and subsequently dried over anhydrous sodium sulfate. The solution was concentrated onto silica and product was eluted with hexane/ethyl acetate (3:1). Purification by distillation in a kugelrohr at 18° C. and 0.5 mmHg yielded 1-(benzo-2,1,3-thiadiazole-5-ylcarbonyl)piperidine, 1 (1.29 g, 87%) as a pale yellow oil. IR: 2920, 2855, 1633, 1478, 1439, 1280, 1223, 1001, 816, and 748 cm−1. 1H NMR (500 MHz): δ 8.06 (1H, d, J=9.1 Hz); 8.02 (1H, s); 7.63 (1H, t, J=9.0 and 1.5 Hz); 3.77 (2H, br s); 3.40 (2H, br s); 1.72 (4H, br s); and 1.57 ppm (2H, br s).

1. additionwere added
2. concentrationconcentrated to one-half the volume
3. customby rotary evaporation
4. additionDry toluene (25 mL) was added
5. temperaturethe reaction solution was heated to 80° C. for 1 hour
6. additionAdditional piperidine (about 0.2 g) was added
7. temperaturethe temperature was increased to 100° C. for 1 hour
8. temperatureto cool to room temperature
9. stirringstirred overnight, at which time it
10. customwas quenched with 10% citric acid and hydrochloric acid
11. additionThe solution was diluted with ethyl acetate
12. washsequentially washed with 10% citric acid, saturated sodium hydrogen phosphate and saturated sodium chloride
13. dry with materialsubsequently dried over anhydrous sodium sulfate
14. concentrationThe solution was concentrated onto silica and product
15. washwas eluted with hexane/ethyl acetate (3:1)
16. customPurification
17. distillationby distillation in a kugelrohr at 18° C.