Processes and intermediates for resolving piperidyl acetamide stereoisomers

• US 20060142583A1
• Filed: 02/23/2006
• Published: 06/29/2006
• Est. Priority Date: 05/22/1997
• Status: Active Grant

• Current Assignee: Sowmianarayanan Ramaswamy, Vikram Khetani, Yalin Luo
• Original Assignee: Sowmianarayanan Ramaswamy, Vikram Khetani, Yalin Luo
• Inventors: Khetani, Vikram, Ramaswamy, Sowmianarayanan, Luo, Yalin
• Granted Patent: US 7,459,560 B2
• Time in Patent Office: Days
• US Class Current: 546/229
• CPC Class Codes: C07D 211/34 with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

Processes and intermediates for preparing 2-substituted piperidines such as 2-substituted d-threo piperidines are provided, including processes and intermediates for resolution of piperidyl acetamide stereoisomers.

Claims

1-14. -14. (canceled)

15. A synthetic process comprising the steps of:

providing a mixture of said d,l-threo piperidyl acetamide stereoisomers having formulas;

wherein R₁ is aryl having about 6 to about 28 carbon atoms;

reacting said stereoisomers with an acid resolving agent having the formula

HO₂CCH[OC(O)R₃]CH[OC(O)R₃]CO₂H

wherein each R₃, independently, is aryl having 6 to about 28 carbon atoms or aralkyl having 7 to about 28 carbon atoms in an organic solvent comprising an alcohol, an alkyl alkanoate, a ketone, or an ether, and thereby forming acid salts; and

physically isolating said acid salts.

16. The process of claim 15 wherein R₁ is phenyl.

17. The process of claim 15 wherein said solvent is an alkyl alcohol having 1 to about 5 carbon atoms.

18. The process of claim 15 wherein said alkyl alcohol is isopropanol.

19. The process of claim 15 further comprising reacting said d-threo acid salts with aqueous base to form said d-threo piperidine acetamide.

20. The process of claim 19 further comprising reacting said d-threo piperidine acetamide with an alcohol having 1 to about 5 carbon atoms in the presence of acid to form a d-threo piperidine acetate.

21. The process of claim 15 wherein said d,l-threo piperidyl acetamide stereoisomers are prepared by reacting a pyridine having formula:

22. The product of the process of claim 15.