Preparation of chiral amides and amines

Patent metadata

Field	Value
Publication number	US-10011559-B2
Application number	US-201715498726-A
Country	US
Kind code	B2
Filing date	Apr 27, 2017
Priority date	Mar 31, 2006
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

This invention provides a convenient method for converting oximes into enamides. The process does not require the use of metallic reagents. Accordingly, it produces the desired compounds without the concomitant production of a large volume of metallic waste. The enamides are useful precursors to amides and amines. The invention provides a process to convert a prochiral enamide into the corresponding chiral amide. In an exemplary process, a chiral amino center is introduced during hydrogenation through the use of a chiral hydrogenation catalyst. In selected embodiments, the invention provides methods of preparing amides and amines that include the 1,2,3,4-tetrahydro-N-alkyl-1-naphthalenamine or 1,2,3,4-tetrahydro-1-naphthalenamine substructure.

First claim

What is claimed:

1. A process for preparing a single trans enantiomer of formula

wherein Q − is an anion; and e is 0 or 1, said process comprising:
a) reacting a ketone of formula:

with hydroxylamine to form an oxime of formula:

b) reacting said oxime with acetic anhydride in the presence of a trialkylphosphine to produce an enamide of formula:

c) reducing said enamide with hydrogen in the presence of a chiral rhodium catalyst to produce a trans acetamide isomer of formula:

containing less than 10% of the corresponding cis isomer; and
d) hydrolyzing said trans acetamide isomer.

2. A process according to claim 1 wherein reacting the ketone with hydroxylamine further includes reacting with sodium acetate in methanol.

3. A process according to claim 1 wherein the chiral rhodium catalyst is a complex of rhodium with a chiral phosphine ligand.

4. A process according to claim 1 wherein hydrolyzing includes acid hydrolysis.

5. A process according to claim 4 wherein the acid hydrolysis includes hydrolyzing with hydrochloric acid.

6. A process according to claim 1 wherein Q − is chlorine.

Assignees

• Sunovion Pharmaceuticals Inc

Inventors

• Zhao Hang
• Koenig Stefan G
• Vandenbossche Charles P
• Singh Surendra
• Wilkinson Harold Scott
• Bakale Roger P

Classifications

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title