反应详情

The mixture, prepared under argon, of 0.280 g of tert-butyl 3-[4-chloro-3-(3-methoxypropoxy)benzyloxy]-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate (Example 31a), 0.080 g of sodium cyanide and 0.005 ml of 15-crown-5 in 2 ml of toluene is initially charged at room temperature with stirring and admixed with 0.75 ml of Ni-catalyst solution (preparation described below). The reaction mixture is stirred at 80° C. for 24 hours and then admixed with a further 0.75 ml of Ni catalyst solution. The reaction mixture is stirred at 80° C. over a further 24 hours and then admixed once more with 0.75 ml of Ni catalyst solution. After stirring for a further 24 hours, the mixture is cooled, admixed with water (30 ml) and extracted with ethyl acetate (2×30 ml). The organic phases are washed with brine (1×30 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.38 (2:1 EtOAc-heptane); Rt=6.10.

1. additionis initially charged at room temperature
2. stirringThe reaction mixture is stirred at 80° C. for 24 hours
3. stirringThe reaction mixture is stirred at 80° C. over a further 24 hours
4. stirringAfter stirring for a further 24 hours
5. temperaturethe mixture is cooled
6. extractionextracted with ethyl acetate (2×30 ml)
7. washThe organic phases are washed with brine (1×30 ml)
8. dry with materialdried over sodium sulphate
9. filtrationfiltered
10. concentrationconcentrated by evaporation