反应详情

温度

80 °C

Diisopropylethylamine (210 ml) is added to a solution of (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-propanamine (311 g; 99.6% ee) in toluene (1200 ml) and phenylchloroformate (150 ml) is then added at 60° C. After two hours of stirring at 80° C., the mixture is cooled down, shaken with a diluted solution of hydrochloric acid, water and a 2% solution of sodium hydrogencarbonate. The organic phase is dried with sodium sulfate and evaporated. The evaporation residue is dissolved in ethanol (300 ml) and a 5M solution of potassium hydroxide (400 ml) is added drop-wise under reflux. After two hours of refluxing, the mixture is evaporated to half the volume, diluted with water (1000 ml) and extracted with toluene (300 ml). The organic phase is dried with sodium sulfate and evaporated. The evaporation residue is dissolved in ethylmethylketone (300 ml) and concentrated HCl (1 mole), diluted with ethylmethylketone (300 ml), is added drop-wise at 0° C.; then the mixture is stirred for two hours. The precipitated crystals are then sucked off. Yield: 250 g (75%), m.p.: 167-169° C. Recrystallization from ethylmethylketone affords colorless crystalline duloxetine hydrochloride, m.p. 170.5-171.5° C. Optical purity: 99.9% ee (CE), chemical purity: 99.9% (HPLC).

1. additionis then added at 60° C
2. temperaturethe mixture is cooled down
3. dry with materialThe organic phase is dried with sodium sulfate
4. customevaporated
5. dissolutionThe evaporation residue is dissolved in ethanol (300 ml)
6. additiona 5M solution of potassium hydroxide (400 ml) is added drop-wise
7. temperatureunder reflux
8. temperatureAfter two hours of refluxing
9. customthe mixture is evaporated to half the volume
10. additiondiluted with water (1000 ml)
11. extractionextracted with toluene (300 ml)
12. dry with materialThe organic phase is dried with sodium sulfate
13. customevaporated
14. dissolutionThe evaporation residue is dissolved in ethylmethylketone (300 ml)
15. additionis added drop-wise at 0° C.
16. stirringthen the mixture is stirred for two hours
17. customRecrystallization from ethylmethylketone