Method for preparing benzoic acid amide compound

Patent metadata

Field	Value
Publication number	US-10723693-B2
Application number	US-201615736406-A
Country	US
Kind code	B2
Filing date	Jun 3, 2016
Priority date	Jun 30, 2015
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

The present invention relates to a method for preparing a benzoic acid amide compound in a high yield by presenting a novel method for preparing a benzyl amine compound to be used as a reactant and delimiting the reaction condition of each step by using the same, and the method is economically advantageous since mass production is possible.

First claim

What is claimed is:

1. A method for preparing a benzoic acid amide derivative of Chemical Formula 1, which is expressed as Reaction Formula 1 and 3 below, and comprises steps of the following S1) to S3):
S1) performing reaction of adamantylation of a benzoic acid compound of Chemical Formula 6 and 1-adamantanol of Chemical Formula 7 under trifluoroacetic acid and concentrated sulfuric acid as an acid catalyst in dichloromethane within the reflux temperature of the dichloromethane to prepare an adamantanyl benzoic acid compound of Chemical Formula 8;
S2) reacting the adamantanyl benzoic acid compound of Chemical Formula 8 and an alkyl haloformate of Chemical Formula 9 in the presence of a base catalyst to prepare an adamantanyl benzoic anhydride of Chemical Formula 3; and
S3) performing an amide coupling reaction of a benzyl amine compound of Chemical Formula 2 or a hydrochloride salt thereof and the adamantanyl benzoic anhydride of Chemical Formula 3 under a base catalyst:

wherein,
a reaction time of the step S1) is 30 min to 2 hours and a yield of the adamantanyl benzoic acid compound of Chemical Formula 8 in the step S1) is 95% or more,
a volume ratio in the step S1) of dichloromethane to reactant consisting of the benzoic acid compound of Chemical Formula 6 and the 1-adamantanol of Chemical Formula 7 is 1:1 to 7:1,
a yield of the benzoic acid amide derivative of Chemical Formula 1 is 75% or more based on the benzyl amine compound of Chemical Formula 2,
R 1 and R 2 are methoxy group,
R 3 and R 4 are the same or different, and are each independently hydrogen, a hydroxyl group, a C 1 to C 5 alkoxyl group, a C 3 to C 6 cycloalkoxyl group, a C 6 to C 20 aryloxy group or a C 1 to C 5 haloalkoxyl group,
R 5 is a C 1 to C 6 alkyl group, and
X is halogen atom,

wherein the benzyl amine compound of Chemical Formula 2 is prepared by steps T1) and T2, expressed as Reaction Formula 2:
T1) preparing a benzaldehyde oxime compound of Chemical Formula 5 by reacting a benzaldehyde compound of Chemical Formula 4 and hydroxyl amine in an aqueous alkaline solution; and
T2) treating the benzaldehyde oxime compound of Chemical Formula 5 with a reducing agent in an aqueous acidic solution:

wherein, R 3 and R 4 are the same or different, and are each independently hydrogen, a hydroxyl group, a C 1 to C 5 alkoxyl group, a C 3 to C 6 cycloalkoxyl group, a C 6 to C 20 aryloxy group, or a C 1 to C 5 haloalkoxyl group.

2. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the R 3 and R 4 are a hydroxyl group.

3. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the base catalyst of S3) is any one selected from the group consisting of triethyl amine, pyridine, N,N-diisopropyl amine, N-methyl morpholine and a combination thereof, and the base catalyst of S2) step is any one selected from the group consisting of triethyl amine, pyridine, N,N-diisopropyl amine, N-methyl morpholine and a combination thereof.

4. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the amide coupling reaction is performed under at least one solvent selected from the group consisting of dichloromethane, chloroform, 1,2-dichloroethane, 1,1,2-trichloroethane, chlorobenzene and a combination thereof.

5. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the aqueous alkaline solution in the T1) step comprises at least one base selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and a combination thereof.

6. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the reducing agent in the T2) step is zinc.

7. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the aqueous acidic solution in the T2) step comprises hydrochloric acid.

Assignees

• Amorepacific Corp

Inventors

• Joo Yung Hyup
• Baek Heung Soo
• Kim Yong Jin
• Shin Hong-Ju
• Lee John Hwan

Classifications

• C07C233/75

  with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring · CPC title

• C07C233/64

  having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07C231/08

  from amides by reaction at nitrogen atoms of 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

• A61K8/44

  Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof · CPC title