GB726078A - Manufacture of indolines - Google Patents

Abstract

The invention comprises Bz-carbamyloxy-indolines of the formula <FORM:0726078/IV (b)/1> wherein R represents a carbamyloxy residue and Alk stands for an alkyl residue, and their salts and quaternary compounds. The carbamyloxy residue can be unsubstituted or be substituted by alkyl, alkenyl, alkylene, cycloalkyl, aryl or heterocyclic radicals. The compounds are produced by converting the corresponding 6-hydroxy-indolines as such or as their salts or quaternary compounds directly or in stages (e.g. with the chlorocarbonic acid ester as an intermediate) into the 6-carbamyloxy-compounds. Quaternation may also be effected after the carbamyloxy group is formed by reaction with, e.g., alkyl halides, alkyl sulphates or toluene sulphonates. Salts with hydrohalic, sulphuric, nitric, phosphoric, thiocyanic, acetic, propionic, oxalic, malonic, succinic, malic, methane sulphonic, ethane sulphonic, hydroxyethane sulphonic, benzene sulphonic and toluene sulphonic acids and salts with therapeutically active acids are referred to. In an example (1) 1-methyl-6-(N-methylcarbamyloxy)-indoline is prepared by reacting 1-methyl-6-hydroxy-indoline with methyl isocyanate in the presence of triethylamine, and the product is converted to 1 : 1-dimethyl-6-(N-methylcarbamyloxy)-indolinium bromide. Also prepared are (2) and (3) 1-methyl-6-(N : N-dimethylcarbamyloxy) - indoline and 1 : 1 - dimethyl - 6 - (N : N - dimethyl - carbamyloxy) - indolinium bromide, in (3) the chlorocarbonic acid ester being formed as an intermediate; (4) 1-methyl-6 - (N : N - diphenyl - carbamyloxy) - indoline by reacting 1-methyl-6-hydroxy-indoline with phosgene and treating the chlorocarbonic acid ester produced with diphenylamine. 1-Methyl-6-hydroxy-indoline is prepared by heating m-acetyl anisidine with sodium in xylene, reacting the product with dimethyl sulphate, evaporating the xylene and treating the product with aqueous potassium hydroxide. The N-methyl-m-anisidine obtained is treated with chloracetyl chloride to give N-methylchloracetyl-m-anisidine, which is heated with aluminium chloride to give 1-methyl-6-hydroxyoxindole, reduction of which with lithium aluminium hydride gives 1-methyl-6-hydroxyindoline.