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ChemicalBook CAS DataBase List 4-Chloronicotinic acid
10177-29-4

4-Chloronicotinic acid synthesis

10synthesis methods
-

Yield:10177-29-4 80%

Reaction Conditions:

Stage #1:4-Chloropyridine with lithium diisopropyl amide in tetrahydrofuran;hexane at -78;Inert atmosphere;
Stage #2:carbon dioxide in tetrahydrofuran;hexane

Steps:

2
As above, 4-chloropyridine 1 is obtained by neutralization of 4-chloropyridine hydrochloride with 10% NaOH as described in SCHMID & WOLKOFF (Canadian Journal of Chemistry, vol. 50, p. 1181-1187, 1972). 4-Chloropyridine 1 (15 mmol) is reacted in THF (250 ml) at -78° C. (nitrogen atmosphere) with 1.2 equivalents of lithium diisopropylamide (1.5 M solution in hexanes containing one equivalent of THF, ALDRICH) (THRASHER et al., Heterocycles, vol. 67, p. 543-547, 2006).Reaction of the resulting anion with dry CO2 allows the formation of 4-chloropyridine-3-carboxylic acid 3 (4-chloronicotinic acid), isolated as a colorless solid with a yield of 60-80% (see GUILLIER et al., J. Org. Chem., vol. 60, p. 292-296, 1995).

References:

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS;INSTITUT CURIE;UNIVERSITE MONTPELLIER 2 SCIENCES ET TECHNIQUES US2011/53975, 2011, A1 Location in patent:Page/Page column 60

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