Method for producing N-butyryl-4-amino-3-methyl-methyl benzoate and the novel compound N-(4-bromo-2-methylphenyl)butanamide

Abstract

The present invention relates to an improved process for preparing methyl N-butyryl-4-amino-3-methylbenzoate and the novel chemical compound N-(4-bromo-2-methylphenyl)butanamide.

1 . A process for preparing methyl N-butyryl-4-amino-3-methylbenzoate, characterized in that o-toluidine is reacted with butyryl chloride to give N-butyryl-2-methylaniline, the latter is brominated to give N-(4-bromo-2-methylphenyl)butanamide and this is converted by reaction with carbon monoxide and methanol in the presence of a palladium catalyst to give methyl N-butyryl-4-amino-3-methylbenzoate.  
     
     
         2 . The process as claimed in  claim 1 , characterized in that the first stage is carried out by initially charging o-toluidine in an inert solvent and then metering in butyryl chloride at temperatures of from 50 to 100° C.  
     
     
         3 . The process as claimed in claims  1  and  2 , characterized in that the second stage is carried out by initially charging N-butyryl-2-methylaniline in acetic acid, adding from 1 to 1.3 molar quantity of elemental bromine together with further acetic acid at from 10 to 80° C., continuing to stir the mixture at from 10 to 80° C. for from 20 minutes to 3 hours, then adding a water quantity of from 0.5 to 5 times the volume, removing the precipitate formed, washing it with water and drying it under reduced pressure.  
     
     
         4 . The process as claimed in  claims 1  to  3 , characterized in that the third step of the process according to the invention is carried out by initially charging N-(4-bromo-2-methylphenyl)butanamide and a palladium catalyst into a pressure vessel, then adding a mixture of methanol, optionally one or more solvents other than methanol and a base, then pressurizing at from 90 to 160° C. to 2-30 bar of carbon monoxide and maintaining this pressure until no more carbon monoxide is taken up.  
     
     
         5 . The process as claimed in  claims 1  to  4 , characterized in that the palladium catalysts used are those of the Pd(P Ph 3 ) 2 X 2  type where Ph=optionally substituted phenyl and X=halogen.  
     
     
         6 . The process as claimed in  claims 1  to  5 , characterized in that a base is added in the third stage.  
     
     
         7 . A process for preparing N-(4-bromo-2-methylphenyl)butanamide, characterized in that o-toluidine is initially charged in an inert organic solvent, butyryl chloride is then metered in at temperatures of from 50 to 100° C., the solvent is removed by adding water to the melt of the amide obtained and distilling it off again, admixing the crude amide thus obtained with a solvent suitable for bromination and adding from 0.45 to 0.95 of bromine per mole of the amide at temperatures of from 10 to 130° C. and, to supplement to 1 mol, an oxidant.  
     
     
         8 . A process for preparing N-(4-bromo-2-methylphenyl)butanamide, characterized in that butyryl chloride is metered in to o-toluidine at from 50 to 100° C., the solvent is removed distillatively, and water is optionally added to the melt of the amide obtained and distilled off again.  
     
     
         9 . The process as claimed in  claim 7 , characterized in that the bromination is carried out by simultaneously metering in the bromine and the oxidant on the one hand and the amide on the other hand with a tolerance of up to 20% in the respective volume flow rates.  
     
     
         10 . N-( 4 -Bromo-2-methylphenyl)butanamide of the formula