Preparation of chiral amides and amines

Patent metadata

Field	Value
Publication number	US-2018016224-A1
Application number	US-201715498726-A
Country	US
Kind code	A1
Filing date	Apr 27, 2017
Priority date	Mar 31, 2006
Publication date	Jan 18, 2018
Grant date	—

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 sub structure.

First claim

1 .- 51 . (canceled)

52 . 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.

53 . A process according to claim 52 wherein said single enantiomer is of formula:

54 . A process according to claim 52 wherein said single enantiomer is of formula:

Assignees

• Sunovion Pharmaceuticals Inc

Inventors

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

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P29/00

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