Process for preparing 2-methyl-N-(2′-methylbutyl)butanamide

Patent metadata

Field	Value
Publication number	US-11629119-B2
Application number	US-202217751974-A
Country	US
Kind code	B2
Filing date	May 24, 2022
Priority date	Jun 7, 2021
Publication date	Apr 18, 2023
Grant date	Apr 18, 2023

Abstract

The present invention provides a process for preparing 2-methyl-N-(2′-methylbutyl) butanamide of the following formula (1):the process comprising: subjecting an α-arylethyl-2-methylbutylamine compound of the following general formula (2): wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, to N-2-methylbutyrylation to form an N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (3): wherein Ar is as defined above, and removing the α-arylethyl group of the resulting compound (3) to form 2-methyl-N-(2′ -methylbutyl)butanamide (1).

First claim

The invention claimed is:

1. A process for preparing 2-methyl-N-(2′-methylbutyl)butanamide of the following formula (1):

the process comprising:
subjecting an α-arylethyl-2-methylbutylamine compound of the following general formula (2):

wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, to N-2-methylbutyrylation to form an N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (3):

wherein Ar is as defined above, and
removing the α-arylethyl group of the resulting compound (3) to form 2-methyl-N-(2′-methylbutyl)butanamide (1).

2. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 1 , the process further comprising
subjecting an α-arylethylamine compound of the following general formula (4):

wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms to N-2-methylbutylation to form the α-arylethyl-2-methylbutylamine compound (2).

3. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 1 ,
wherein the N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound (3) is a (2S)-N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (2S)-(3):

wherein the wedged bond represents an absolute configuration, and Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms and
wherein the 2-methyl-N-(2′-methylbutyl)butanamide (1) is (2S)-2-methyl-N-(2′-methylbutyl)butanamide of the following general formula (2S)-(1):

4. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 2 ,
wherein the α-arylethyl-2-methylbutylamine compound (2) is a (2S)-α-arylethyl-2-methylbutylamine compound of the following general formula (2S)-(2):

wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms,
wherein the N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound (3) is a (2′S)-N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (2′S)-(3):

wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, and
wherein 2-methyl-N-(2′-methylbutyl)butanamide (1) is (2′S)-2-methyl-N-(2′-methylbutyl)butanamide of the following formula (2′S)-(1):

5. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 2 ,
wherein the α-arylethyl-2-methylbutylamine compound (2) is a (2S)-α-arylethyl-2-methylbutylamine compound of the following general formula (2S)-(2):

wherein the wedged bond represents an absolute configuration, and Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms,
wherein the N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound (3) is a (2S,2′S)-N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (2S,2′S)-(3):

wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, and
wherein 2-methyl-N-(2′-methylbutyl)butanamide (1) is (2S,2′S)-2-methyl-N-(2′-methylbutyl)butanamide of the following formula (2S,2′ S)-(1):

6. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 1 ,
the process further comprising, prior to the N-2-methylbutyrylation, isolating a mixture of diastereomers of an α-arylethylamine compound of the following general formulae (2R*,αR*)-(2) and (2S*, 60 R*)-(2):

wherein the hashed bond and the bold bonds represent a relative configuration, and Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, from the α-arylethyl-2-methylbutylamine compound (2), and
subjecting at least one of the α-arylethylamine compounds (2R*,αR*)-(2) and (2S*,αR*)-(2) isolated from the mixture of diastereomers to the N-2-methylbutyrylation and the removal of the α-arylethyl group.

7. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 3 ,
wherein the α-arylethyl-2-methylbutylamine compound (2) is a (2S)-α-arylethyl-2-methylbutylamine compound of the following general formula (2S)-(2):

wherein the wedged bond represents an absolute configuration, and Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms,
wherein the N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound (3) is a (2S,2′S)-N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (2S,2′S)-(3):

wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, and
wherein 2-methyl-N-(2′-methylbutyl)butanamide (1) is (2S,2′S)-2-methyl-N-(2′-methylbutyl)butanamide of the following formula (2S,2′S)-(1):

8. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 4 ,
wherein the α-arylethyl-2-methylbutylamine compound (2) is a (2S)-α-arylethyl-2-methylbutylamine compound of the following general formula (2S)-(2):

wherein the wedged bond represents an absolute configuration, and Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms,
wherein the N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound (3) is a (2S,2′S)-N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (2S,2′S)-(3):

wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, and
wherein 2-methyl-N-(2′-methylbutyl)butanamide (1) is (2S,2′S)-2-methyl-N-(2′-methylbutyl)butanamide of the following formula (2S,2′S)-(1):

9. The process for preparing 2-methyl-N-(2′-methylbutyl)butanamide (1) according to claim 2 ,
the process further com

Assignees

• Shinetsu Chemical Co

Inventors

• Kinsho Takeshi
• Nagae Yusuke
• Tsukaguchi Shogo
• Kutsuwada Yasuhiko
• Hojo Tatsuya
• Watanabe Takeru

Classifications

• C07C231/14 Primary

  by formation of carboxamide groups together with reactions not involving the carboxamide groups · CPC title

• C07C231/02 Primary

  from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07C231/20

  by separation of optical isomers · CPC title

• C07C209/14

  by substitution of hydroxy groups or of etherified or esterified hydroxy groups · CPC title