反应详情

2.23 g (60 mmol) of sodium borohydride were added spatula-wise to a suspension of 9.7 g (39 mmol) of (RS)-4-(4-chloro-phenyl)-1-methyl-3-propyl-1,2,3,6-tetrahydro-pyridine in 80 ml of 1,2-dimethoxyethane in such a manner that the temperature did not rise above 35° C. Subsequently, 13.2 ml of boron trifluoride etherate dissolved in 15 ml of 1,2-dimethoxyethane were added dropwise during 45 minutes and thereafter the reaction mixture was stirred at room temperature for 2 hours. Subsequently, firstly a solution of 15.65 g (277 mmol) of potassium hydroxide dissolved in 60 ml of water was slowly added dropwise at about 30° C. and thereafter within 15 minutes 11.2 ml of a 30% hydrogen peroxide solution was added, with the temperature rising to 40° C. Subsequently, the mixture was boiled under reflux for 2.5 hours. For the working-up, the cooled reaction mixture was filtered over Dicalit and this was rinsed with ethyl acetate. The solution obtained was treated with 100 ml of ethyl acetate and 100 ml of water, the organic phase was separated and then the aqueous phase was back-extracted with 100 ml of ethyl acetate. The combined organic phases were dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 95:5 mixture of methylene chloride and methanol as the eluent. There were obtained 8.64 g (73% of theory) of (3RS,4SR, 5RS)-4-(4-chloro-phenyl)-1-methyl-5-propyl-piperidin-3-ol as a colourless solid; MS: 267 (M)+.

1. customdid not rise above 35° C
2. additionwere added dropwise during 45 minutes
3. additionwas slowly added dropwise at about 30° C.
4. customrising to 40° C
5. temperatureunder reflux for 2.5 hours
6. customthe cooled reaction mixture
7. filtrationwas filtered over Dicalit
8. washthis was rinsed with ethyl acetate
9. customThe solution obtained
10. customthe organic phase was separated
11. extractionthe aqueous phase was back-extracted with 100 ml of ethyl acetate
12. dry with materialThe combined organic phases were dried over sodium sulphate
13. customevaporated under reduced pressure
14. customFor purification
15. customthe crude product was chromatographed on silica gel using
16. additiona 95:5 mixture of methylene chloride and methanol as the eluent