CH494224A - 1-benzoyl-2-methyl-3-indolyl acetic acid derivs - Google Patents

Abstract

Improved method for R = MeO or Me2N Z = Cl CO- N.B. II and other unspecified intermediates are new.

Description

  

  
 



  Process for the production of indole acids
The present invention relates to a process for the preparation of indolylacetic acid derivatives of the formula (I):
EMI1.1
 wherein R is methoxy or dimethylamino. These compounds are described and claimed in U.S. Patent No. 3,161,654 dated December 15, 1964.



   In the patent just mentioned, 1-pw-chlorobenzoyl-2-methyl-3-indolylacetic acid derivatives are prepared by a series of reactions, with 2-methyl-3-indolylacetic acids being dehydrated to the corresponding anhydride; treating the anhydrides with t-butyl alcohol to form the corresponding t-butyl ester; the t-butyl ester is then acylated in position 1 with p -chlorobenzoyl chloride; and the obtained l-acylates are converted into the derivatives of free acetic acid by a pyrolysis process.



   The present inventive method for the preparation of the above compound I is characterized in that a ketimine of the formula:
EMI1.2
 with an acid catalyst, e.g. Subjecting para-toluenesulfonic acid, preferably under anhydrous conditions, to a ring closure reaction, a compound of the formula I being formed. The reaction is best brought to completion by heating, preferably under reflux conditions. The product of the formula I can be recovered from the reaction mixture as a precipitate. In the case of a product of the formula I, where R is dimethylamino, it may be necessary to adjust the pH to about 4 in order to initiate the precipitation.



  By drying the precipitate and recrystallizing it from a solvent e.g. a lower alkanol, e.g. t-butanol, the desired product is obtained in pure form.



   This method according to the invention is illustrated by two examples.



   Example I.
2.5 g of 3- (2'-p-chlorobenzamido-5'-methoxyphenyl) levulinic acid ketimine are dissolved in 20 ml of 95% acetic acid containing 100 mg of p-toluenesulfonic acid. The mixture is refluxed under nitrogen for 2 hours and then cooled to room temperature. 20 ml of water are added. The precipitate is collected by filtration, freed of acid by washing and recrystallized from a 1: 1 mixture of ethyl acetate and hexane to give 1-p-chlorobenzoyl-2-methyl-5-methoxy-3-indolylacetic acid.

 

   Example 2
3.0 g of 3- (2'-p-chlorobenzamido-5'-dimethylaminophenyl) levulinic acid ketimine are dissolved in 20 ml of acetic acid containing 3 g of toluenesulfonic acid. The mixture is refluxed under nitrogen for 2 hours and then concentrated in vacuo to a small volume and diluted with 100 ml of cold water. The pH of the mixture is adjusted to 4 by the addition of 10% aqueous sodium hydroxide, whereby 1-p-chlorobenzoyl-2-methyl-5-dimethylamino-3-indolylacetic acid is precipitated.

 

Claims (1)

PATENT CLAIM Process for the preparation of a compound of the formula: EMI2.1 wherein R is methoxy or dimethylamino, characterized in that a compound of the formula: EMI2.2 undergoes an acid catalyzed ring closure reaction. Merck & Co., Inc. Representative: Bovard & Cie., Bern Note from the Federal Office for Intellectual Property: If parts of the description are not in accordance with the definition of the invention given in the patent claim, it should be remembered that according to Art. 51 of the Patent Act, the patent claim is decisive for the material scope of the patent.