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

HRID 512706Notes

Reaction equation

HRID 512706 reaction equation
Cl.[Cl:2][C:3]1[CH:7]=[C:6](C(O)=O)[N:5]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:4]=1>[Cu]=O.CN(C)C=O>[Cl:2][C:3]1[CH:7]=[CH:6][N:5]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:4]=1

Participants

4

Reactant 1

HCID 1180217823-Chloro-1-(pyridine-3-yl)-1H-pyrazole-5-carboxylic acid hydrochloride

Product 1

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

Reagents, catalysts & solvents 2

HCID 14829Copper oxideCatalystHCID 6228DimethylformamideSolvent

Procedure

In step e of Scheme 4, 3-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid hydrochloride (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 (See “CE-5”) did not yield the desired product.

Sources & evidence

ORD record
ord-052165b317514a4fb998b511a6bd1c3a
Source dataset
uspto-grants-2015_08
Patent number
US09102654B2

Reaction notes

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