Amine-boranes as bifunctional reagents for direct amidation of carboxylic acids

Patent metadata

Field	Value
Publication number	US-12071393-B2
Application number	US-202117407276-A
Country	US
Kind code	B2
Filing date	Aug 20, 2021
Priority date	Aug 21, 2020
Publication date	Aug 27, 2024
Grant date	Aug 27, 2024

Abstract

The present invention generally relates to a process for selective and direct activation and subsequent amidation of aliphatic and aromatic carboxylic acids to afford an amide R 3 CONR 1 R 2 . That the process is capable of delivering gaseous or low-boiling point amines provides a major advantage over existing methodologies, which involves an intermediate of triacyloxyborane-amine complex [(R 3 CO 2 ) 3 —B—NHR 1 R 2 ]. This procedure readily produces primary, secondary, and tertiary amides, and is compatible with the chirality of the acid and amine involved. The preparation of known pharmaceutical molecules and intermediates has also been demonstrated.

First claim

The invention claimed is:

1. A triacyloxyborane-amine complex comprising [(R 3 CO 2 ) 3 —B −1 —N +1 H(R 1 )R 2 ], wherein R 3 is an aryl, each of which is optionally substituted; R 1 and R 2 are, independently, hydrogen, an alkyl, or an aryl, wherein said alkyl or aryl are optionally substituted and said R 1 and R 2 are not both an aryl, an alkyl, or a hydrogen at the same time.

2. The triacyloxyborane-amine complex [(R 3 CO 2 ) 3 —B −1 —N +1 H(R 1 )R 2 ], according to claim 1 , wherein said triacyloxyborane-amine complex [(R 3 CO 2 ) 3 —B −1 —N +1 H(R 1 )R 2 ] is manufactured as following:
a. preparing an amine-borane (R 1 )R 2 N—BH 3 from an amine R 1 R 2 NH; wherein R 1 and R 2 are, independently, hydrogen, an alkyl, or an aryl, wherein said alkyl or aryl are optionally substituted and said R 1 and R 2 are not both an aryl, and alkyl, or a hydrogen at the same time;
b. preparing a carboxylic acid R 3 COOH, wherein R 3 is an aryl, which is optionally substituted;
c. dissolving one equivalent of said amine-borane and about three equivalents of said carboxylic acid in xylenes or a compatible solvent to afford a reaction mixture; and
d. heating said reaction mixture to about 90-100° C. for about 1 hour to afford said said triacyloxyborane-amine complex [(R 3 CO 2 ) 3 —B −1 —N +1 H(R 1 )R 2 ].

3. A product manufactured using the triacyloxyborane-amine complex according to claim 1 .

4. An active pharmaceutical ingredient manufactured using the triacyloxyborane-amine complex according to claim 1 .

Assignees

• Purdue Research Foundation

Inventors

• Ramachandran Padinjaremadhom V
• Hamann Henry J

Classifications

• C07C233/05

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07D213/82

  in position 3 · CPC title

• C07D295/192

  from aromatic carboxylic acids · CPC title

• C07C233/08

  with carbon atoms of carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings · CPC title

• C07C323/41

  Y being a hydrogen or an acyclic carbon atom · CPC title