反应详情

Sodium hydride (1.5 g, 37 mmol, 60% oil dispersion) was added portionwise to a stirred solution of 3-phenyl-1-propanol (5.0 g, 37 mmol) in toluene (25 ml) placed under an atmosphere of nitrogen. The mixture was stirred for 30 minutes at ambient temperature and then heated at reflux for 45 minutes. The reaction mixture was allowed to cool and another portion of sodium hydride (1.5 g, 37 mmol, 60% oil dispersion) was added followed by toluene (25 ml). The suspension was heated at reflux for 15 minutes and allowed to cool. Keeping the temperature below 40° C. 1-(2-bromoethyl)-3piperidinecarboxylic acid ethyl ester hydrobromide (12.6 g, 37 mmol, EP 374801) was added portionwise. The reaction mixture was stirred for 3 days and then left for 3 weeks. The mixture was poured into water (200 ml) and extracted with ethyl acetate (100 ml). The phases were separated and the organic phase was extracted with 5% citric acid solution (3×100 ml). The combined acidic phases were extracted with ethyl acetate (100 ml) which was discarded. 4N sodium hydroxide was added to the aqueous phase until pH 8 and then it was extracted with ethyl acetate (2×100 ml). The combined organic extracts were washed with saturated sodium bicarbonate solution and dried (Na2SO4). The solvent was evaporated in vacuo to give 3.2 g of 1-(2-(3-phenyl-1-propyloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil.

1. temperatureheated
2. temperatureat reflux for 45 minutes
3. temperatureto cool
4. temperatureThe suspension was heated
5. temperatureat reflux for 15 minutes
6. temperatureto cool
7. customthe temperature below 40° C
8. stirringThe reaction mixture was stirred for 3 days
9. waitleft for 3 weeks
10. extractionextracted with ethyl acetate (100 ml)
11. customThe phases were separated
12. extractionthe organic phase was extracted with 5% citric acid solution (3×100 ml)
13. extractionThe combined acidic phases were extracted with ethyl acetate (100 ml) which
14. addition4N sodium hydroxide was added to the aqueous phase until pH 8
15. extractionit was extracted with ethyl acetate (2×100 ml)
16. washThe combined organic extracts were washed with saturated sodium bicarbonate solution
17. dry with materialdried (Na2SO4)
18. customThe solvent was evaporated in vacuo