Potassium Carbonate → CP-99994

Borane dimethylsulfide in tetrahydrofuran (2M, 158 ml, 315 mmole) was added to a solution of cis-5-(2-methoxybenzylamino)-2-oxo-6-phenylpiperidine (19.6 g, 63.0 mmole) in tetrahydrofuran (500 ml) under nitrogen and the reaction mixture was heated at reflux for 18 hours. At the end of this period, the reaction mixture was cooled and the excess borane dimethylsulfide was cautiously decomposed by dropwise addition of methanol. The contents of the reaction mixture were then concentrated under vacuum. Ethanol (500 ml) and powdered potassium carbonate (17.5 g, 126 mmole) were added to the residue and the reaction mixture was heated at reflux (18 hours). Then the reaction mixture was concentrated under vacuum and the residue was extracted with methylene chloride (4×250 ml) and dried (anhydrous magnesium sulfate). The organic solvents were removed under vacuum to afford a residue which was dissolved in a minimum amount of methylene chloride. To this solution was added excess hydrochloric acid/ether, thus precipitating the dihydrochloride salt of cis-3-(2-methoxybenzylamino)-2-phenylpiperidine, which was isolated by filtration. This was heated at reflux in chloroform (400 ml) for 3 hours and filtered to give the essentially pure hydrochloride salt of the title compound (22.4 gms, m.p. 245° C., 96%), which was crystallized from a mixture of hot methanol-ethanol to afford a white crystalline solid (19.2 gms, 83%).

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 18 hours
3. temperatureAt the end of this period, the reaction mixture was cooled
4. concentrationThe contents of the reaction mixture were then concentrated under vacuum
5. temperaturethe reaction mixture was heated
6. temperatureat reflux (18 hours)
7. concentrationThen the reaction mixture was concentrated under vacuum
8. extractionthe residue was extracted with methylene chloride (4×250 ml)
9. dry with materialdried (anhydrous magnesium sulfate)
10. customThe organic solvents were removed under vacuum
11. customto afford a residue which
12. customthus precipitating the dihydrochloride salt of cis-3-(2-methoxybenzylamino)-2-phenylpiperidine
13. customwhich was isolated by filtration
14. temperatureThis was heated
15. filtrationfiltered

ORD record

ord-c12bc3cb48c64d858d083d1ff626869a

Source dataset

uspto-grants-1993_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05232929