Patent ID: 6111112
Filing Date: 2000-08-29
Classification: C07D

Abstract:
A method for making 3-amino-2-chloro-4-methylpyridine comprising the following steps:(a) reacting malononitrile with acetone to yield isopropylidenemalononitrile;(b) condensing the isopropylidenemalononitrile so produced with triethyl orthoformate in acetic acid anhydride yield a mixture of 2-(3-ethoxy-1-methyl-(E)-2-propenylidene)malononitrile and 2-(3,3-diethoxy-1-methylpropylidene)malononitrile;(c) treating the mixture of 2-(3-ethoxy-1-methyl-(E)-2-propenylidene)malononitrile and 2-(3,3-diethoxy-1-methylpropylidene)malononitrile so produced with anhydrous ammonia in ethanol, to effect ring closure, thus producing 2-amino-4-methyl-pyridine-carbonitrile;(d) reacting the 2-amino-4-methyl-pyridine-carbonitrile so produced with sodium nitrite, to yield the diazonium salt thereof, and thereafter treating the diazonium salt in situ with water to yield 2-hydroxy-4-methyl-3-cyanopyridine;(e) reacting the 2-hydroxy-4-methyl-3-cyanopyridine so produced with phosphorus oxychloride to yield 2-chloro-4-methyl-3-pyridinecarbonitrile;(f) treating the 2-chloro-4-methyl-3-pyridinecarbonitrile so produced with concentrated sulfuric acid, to effect hydrolysis, to yield 2-chloro-4-methyl-3-carboxamide; and,(g) converting the 2-chloro-4-methyl-3-carboxamide so produced, via the Hofmann reaction (treatment with solution of chlorine or bromine in excess sodium hydroxide), to 3-amino-2-chloro-4-methylpyridine.