Process for the preparation of 3-(3-chloro-1H-pyrazol-1-yl)pyridine
3-(3-chloro-1H-pyrazol-1-yl)pyridine is prepared by cyclizing 3-hydrazinopyridine-.dihydrochloride with a dialkyl maleate to provide an alkyl 5-oxo-2-(pyridin-3-yl)pyrazolidine-3-carboxylate, by chlorinating to provide an alkyl 3-chloro-1-(pyridin-3-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate, by oxidizing to provide an alkyl 3-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylate, by converting the ester to the carboxylic acid by hydrolysis to provide 3-chloro-1 -(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid hydrochloride, and by removing the carboxylic acid by a decarboxylation reaction.
1. A process for preparing an alkyl 5-oxo-2-(pyridin-3-yl)pyrazolidine-3-carboxylate (10a)
comprising,
treating 3-hydrazinopyridine.dihydrochloride
with a dialkyl maleate
in a (C 1 -C 4 ) aliphatic alcohol at a temperature of about 25° C. to about 100° C. in the presence of an alkali metal (C 1 -C 4 ) alkoxide, wherein R is (C 1 -C 4 ) alkyl.
2. The process of claim 1 , wherein the amount of dialkyl maleate is a stoichiometric amount.
3. The process of claim 1 , wherein the amount of dialkyl maleate is about a 1.5 fold to about a 2 fold excess.
4. The process of claim 1 , wherein the amount of alkali metal (C 1 -C 4 ) alkoxide is about a 2 fold to about a 5 fold excess.
5. The process of claim 1 , wherein the (C 1 -C 4 ) aliphatic alcohol is ethanol.
6. The process of claim 1 , wherein R is ethyl.
7. The process of claim 1 , wherein the alkali metal (C 1 -C 4 ) alkoxide is sodium ethoxide.
8. The process of claim 1 , wherein the (C 1 -C 4 ) aliphatic alcohol is ethanol, R is ethyl and the alkali metal (C 1 -C 4 ) alkoxide is sodium ethoxide.