Process for the preparation of (2r)-methyl-4,4,4-trifluorobutylamine the intermediate 4,4,4-trifluoro-2-methyl-n-(s)-1-phenylethyl butyramide and a process for the preparation of (r)-4-5-(n-4,4,4- trifluoro-2- methylbutyl carbamoyl-1- methylindol-3-ylmethyl-3- methoxy-n-o-tolylsulphonylbenzamide

摘要

A process for the preparation of (2R)-methyl-4,4,4-trifluorobutylamine, or an acid addition salt thereof which comprises a) acylating an optically active amine with 2-methyl-4,4,4-trifluorobutanoic acid or a reactive derivative thereof to afford a butyramide; b) separating (R)-diastereomeric butyramide from (S)-diastereomeric butyramide; and c) converting the (R)-diastereomeric butyramide into the desired (2R)-methyl-4,4,4-trifluorobutylamine, or an acid addition salt thereof. The product may be acylating with a carboxylic acid of formula III CHEM wherein U is carboxy, or a reactive derivative thereof to afford (R)-4-[5-(N-[4,4,4-trifluoro-2-methylbutyl]carbamoyl)-1-methylindol-3- yl-methyl]-3-methoxy-N-o-tolylsulpho nylbenzamide. The indole is useful as a leukotriene antagonist, for example in the treatment of asthma or allergic rhinitis.