Toluene → Tert-butyl 3-(2-amino-4-methylbenzyloxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Temperatur

80 °C

The mixture of 0.800 g of tert-butyl 3-(2-bromo-4-methylbenzyloxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate, 0.250 ml of benzophenone imine, 0.0037 g of dipalladiumtris(dibenzylidenacetone)-chloroform complex, 0.0051 g of (R)-(+)-2,2′-bis(diphenylphosphine)-1,1′-binaphthyl and 0.168 g of sodium tert-butoxide is admixed with 6.0 ml of toluene and stirred under argon at 80° C. over 72 hours. The reaction mixture is cooled, admixed with brine (20 ml) and extracted with ethyl acetate (2×80 ml). The organic phases are dried over sodium sulphate, filtered and concentrated by evaporation. The residue is dissolved in 6.0 ml of methanol, admixed with 0.090 g of 5% Pd/C and 1.15 g of ammonium formate, and stirred at 60° C. over 72 hours. The reaction mixture is diluted with methanol (20 ml) and clarified by filtration, and the filtrate is concentrated by evaporation. The residue is admixed with 0.1M NaOH (100 ml) and extracted with ethyl acetate (2×100 ml). The organic phases are washed successively with 0.1M NaOH (100 ml) and brine (100 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.30 (1:2 EtOAc-heptane); Rt=5.32.

1. temperatureThe reaction mixture is cooled
2. extractionextracted with ethyl acetate (2×80 ml)
3. dry with materialThe organic phases are dried over sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated by evaporation
6. dissolutionThe residue is dissolved in 6.0 ml of methanol
7. stirringstirred at 60° C. over 72 hours
8. additionThe reaction mixture is diluted with methanol (20 ml)
9. filtrationclarified by filtration
10. concentrationthe filtrate is concentrated by evaporation
11. extractionextracted with ethyl acetate (2×100 ml)
12. washThe organic phases are washed successively with 0.1M NaOH (100 ml) and brine (100 ml)
13. dry with materialdried over sodium sulphate
14. filtrationfiltered
15. concentrationconcentrated by evaporation

ORD-Eintrag

ord-a5bfa7cda5c843e08eac124c251b908f

Quelldatensatz

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07790715B2