反应详情

20 g NaH (60% in mineral oil) is suspended in 500 ml of dry DMF under a blanket of dry nitrogen. 124 g 5-(3,4-dimethoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (compound C1) is added in portions and stirred for an additional 30 min at RT. The solution becomes slightly yellow. 168 g tert-butyl 4-{[(4-methylphenyl)sulfonyl]oxy}piperidine-1-carboxylate (compound E1) in 150 ml of DMF is added in one portion and the mixture is placed in a preheated oil bath (140° C.) and heated for 1.0 hr. The mixture is cooled to 50° C. (part of the sodium toluenesulfonate crystallizes) 1000 ml of water is added and the mixture is extracted with 200 ml of ethyl acetate (five times). The combined organic layers are washed with 100 ml of water (five times), 50 ml of brine, dried over MgSO4 and concentrated in vacuo. The oil obtained is dissolved in 300 ml of ethanol and 300 ml of 1M H2SO4 is added and heated at reflux for 60 min. The ethanol is removed in vacuo, 200 ml of water is added and washed with 100 ml DCM (five times). The aqueous layer is basified with 40 g NaOH in 250 ml water and extracted with 200 ml of dichloromethane (three times), dried over MgSO4 and concentrated in vacuo. The oil is suspended in 300 ml of ethanol with 30 ml of concentrated hydrochloric acid and heated until it dissolves. Cooling in ice causes precipitation. The collected precipitates are dried resulting in the hydrochloride salt of the title compound. (compound B1*HCl)

1. customthe mixture is placed in a preheated oil bath
2. temperature(140° C.) and heated for 1.0 hr
3. customcrystallizes) 1000 ml of water
4. additionis added
5. extractionthe mixture is extracted with 200 ml of ethyl acetate (five times)
6. washThe combined organic layers are washed with 100 ml of water (five times), 50 ml of brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe oil obtained
10. temperatureheated
11. temperatureat reflux for 60 min
12. customThe ethanol is removed in vacuo, 200 ml of water
13. additionis added
14. washwashed with 100 ml DCM (five times)
15. extractionextracted with 200 ml of dichloromethane (three times)
16. dry with materialdried over MgSO4
17. concentrationconcentrated in vacuo
18. temperatureheated until it
19. dissolutiondissolves
20. temperatureCooling in ice
21. customprecipitation
22. customThe collected precipitates
23. customare dried