3-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid → 3-(3-chloro-1H-pyrazol-1-yl)pyridine

HRID 1773172Notes

Reaction equation

HRID 1773172 reaction equation
[Cl:1][C:2]1[CH:6]=[C:5](C(O)=O)[N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1>[Cu]=O.CN(C)C=O>[Cl:1][C:2]1[CH:6]=[CH:5][N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1

Participants

4

Reactant 1

HCID 917544803-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 674995403-(3-chloro-1H-pyrazol-1-yl)pyridine

Reagents, catalysts & solvents 2

HCID 14829Copper oxideCatalystHCID 6228DimethylformamideSolvent

Procedure

In step d of Scheme 2, 3-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid (6e) is decarboxylated in the presence of copper (II) oxide in polar solvents such as N,N-dimethylformamide at temperatures from about 80° C. to about 140° C. to yield 3-(3-chloro-1H-pyrazol-1-yl)pyridine (5b). It was surprisingly discovered that this decarboxylation only occurs in the presence of copper (II) oxide. Several known decarboxylation agents from the literature such as, for example, hydrochloric acid (See alternate synthetic route, Example 14), sulfuric acid, and palladium (II) trifluoroacetate/trifluoroacetic acid (Pd(TFA)2/TFA) (See “CE-5”) did not yield the desired product.

Sources & evidence

ORD record
ord-500dd8d3010d449eaf715960c95b8f1b
Source dataset
uspto-grants-2016_02
Patent number
US09255083B2

Reaction notes

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