Preparation of intermediates for the synthesis of...

C - Chemistry – Metallurgy – 07 – D

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C07D 211/02 (2006.01) C07D 211/90 (2006.01)

Patent

CA 2701272

4-(2, 3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-3- pyridinecarboxylic acid, a key intermediate in the synthesis of the cardiovascular calcium channel blocker drug 3-butanoyloxymethoxycarbonyl-5- methoxycarbonyl-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine, of purity greater than 97% and essentially free of the corresponding diacid, is prepared by a process involving selective precipitation of its carboxylate via addition of concentrated solutions of alkali metal salts. Similar intermediate mono-carboxylic acids useful in the synthesis of other unsymmetrically substituted dihydropyrine drugs such as nisoldipine, nitrendipine and nimodipine can be similarly prepared and purified.

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