反应详情

120 g (620 mmol) 4-piperidin-4-yl-butan-1-ol hydrochloride are suspended in 400 ml 3,4-dihydro-2H-pyran and added to 1.5 g pyridinium tosylate and 5 ml 8 M methaneolic hydrochloric acid. This is stirred for three hours and left to stand at RT overnight. After addition of 5 g potassium carbonate, this is concentrated under vacuum to dryness. The resulting 4-[4-Tetrahydro-pyran-2-yloxy)-butyl]-piperidine is dissolved in 500 ml acetonitrile without further purification and added to 193 g (742 mmol) diphenylmethyl bromide (95%) and 160 g (1157 mmol) potassium carbonate and stirred for three days at RT. The mixture is filtered and the filtrate is stirred with a further 20 g (76.8 mmol) diphenylmethyl bromide (95%) and 16 g (115.8 mmol) potassium carbonate for one day at RT. The mixture is filtered and the solvent is removed under vacuum. The resulting 1-diphenylmethyl-4-[4-(tetrahydro-pyran-2-yloxy)-butyl]-piperidine is dissolved in 700 ml methanol without further purification, added to 120 ml conc. hydrochloric acid and the mixture is left to stand for two days at RT. Subsequently, the solvent is drawn off under vacuum, the residue is taken up with 1500 ml water and extracted with 1500 ml acetic acid ethyl ester. The organic phase is discarded and the aqueous phase is made alkaline with 95 g sodium hydroxide and extracted with 700 ml acetic acid ethyl ester. After washing the organic phase with 200 ml water, this is dried over sodium sulfate and the solvent is removed under vacuum The brown oil is dried under high-vacuum and further processed without additional purification. Yield 145 g (72%).

1. waitleft
2. waitto stand at RT overnight
3. concentrationthis is concentrated under vacuum to dryness
4. dissolutionThe resulting 4-[4-Tetrahydro-pyran-2-yloxy)-butyl]-piperidine is dissolved in 500 ml acetonitrile without further purification
5. stirringstirred for three days at RT
6. filtrationThe mixture is filtered
7. filtrationThe mixture is filtered
8. customthe solvent is removed under vacuum
9. dissolutionThe resulting 1-diphenylmethyl-4-[4-(tetrahydro-pyran-2-yloxy)-butyl]-piperidine is dissolved in 700 ml methanol without further purification
10. additionadded to 120 ml conc. hydrochloric acid
11. waitthe mixture is left
12. waitto stand for two days at RT
13. extractionextracted with 1500 ml acetic acid ethyl ester
14. extractionextracted with 700 ml acetic acid ethyl ester
15. washAfter washing the organic phase with 200 ml water
16. dry with materialthis is dried over sodium sulfate
17. customthe solvent is removed under vacuum The brown oil
18. customis dried under high-vacuum
19. customfurther processed without additional purification