反应详情

To a suspension of NaBH4 (310 mg, 0.30 equivalents) in aqueous NaOH (30% w/w) was added 3-dimethylamino-1-thiophen-2-yl-propan-1-one hydrochloride (5.95 gm, 27.2 mmol) in portions, over 30 minutes. The cloudy mixture was stirred at room temperature. After 1 h a second portion of NaBH4 (310 mg, 0.30 equivalents) was added. The reaction mixture was stirred at room temperature under nitrogen. After approximately 20 h, HPLC showed complete conversion, and the cloudy mixture was cooled to 0° C. The reaction mixture was carefully acidified with 37% HCl (aq.) to pH 1, while maintaining the temperature less than 10° C. The cloudy mixture gradually turned homogenous. The reaction mixture was washed with toluene (2×20 mL). The aqueous layer was cooled to 0° C., and carefully added 30% NaOH (aq.) to pH 12, while maintaining the temperature less than 20° C. There was formation of a white precipitate. The aqueous solution was extracted with warm toluene (45° C.; 3×80 mL). The toluene was removed under reduced pressure (bath temperature 45° C.). The white solid was taken up in ethylcyclohexane (20 mL) and heated to 70° C. until a clear homogenous mixture was obtained. The solution was stirred at 70° C. for 2 h. The solution was cooled to 0° C. After approximately 45 minutes at 0° C., the white solid was filtered and washed with ice-cold ethylcyclohexane (2×15 mL). The white solid was dried under vacuum at 40° C. for 18 h to give 3.6 gm (72%) of 2 as a racemic mixture.

1. stirringThe reaction mixture was stirred at room temperature under nitrogen
2. waitAfter approximately 20 h
3. temperaturethe cloudy mixture was cooled to 0° C
4. temperaturewhile maintaining the temperature less than 10° C
5. washThe reaction mixture was washed with toluene (2×20 mL)
6. temperatureThe aqueous layer was cooled to 0° C.
7. temperaturecarefully added 30% NaOH (aq.) to pH 12, while maintaining the temperature less than 20° C
8. extractionThe aqueous solution was extracted with warm toluene (45° C.; 3×80 mL)
9. customThe toluene was removed under reduced pressure (bath temperature 45° C.)
10. temperatureheated to 70° C. until a clear homogenous mixture
11. customwas obtained
12. stirringThe solution was stirred at 70° C. for 2 h
13. temperatureThe solution was cooled to 0° C
14. waitAfter approximately 45 minutes at 0° C.
15. filtrationthe white solid was filtered
16. washwashed with ice-cold ethylcyclohexane (2×15 mL)
17. customThe white solid was dried under vacuum at 40° C. for 18 h