Water → 2'-methyl-2'H-[1,3']bipyrazolyl-4'-carboxylic acid ethyl ester

HRID 12824Notes

Reaction equation

[H-].[Na+].[NH:3]1[CH:7]=[CH:6][CH:5]=[N:4]1.[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[N:15][N:16]([CH3:19])[C:17]=1Cl)=[O:12])[CH3:9].O>CN(C=O)C.C(OCC)(=O)C>[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[N:15][N:16]([CH3:19])[C:17]=1[N:3]1[CH:7]=[CH:6][CH:5]=[N:4]1)=[O:12])[CH3:9]

Participants

Conditions

Temperature: 40 °C

Procedure

Sodium hydride (60% in oil; 767 mg, 19 mmol) was added to a solution of pyrazole (1.36 g, 20 mmol) in dry DMF (40 mL) under nitrogen at 0° C. in an ice-water bath and the mixture was heated to 40° C. for 1 h. 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.89 g, 10 mmol) was added and the mixture was heated to 100° C. overnight and then cooled. Water and ethyl acetate were added, the organic layer was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic phases were concentrated in vacuo and the residue was purified by flash silica chromatography eluting with a gradient of 0-20% ethyl acetate/hexanes, then 20% ethyl acetate/hexanes to give 2′-methyl-2′H-[1,3′]bipyrazolyl-4′-carboxylic acid ethyl ester (0.2 g, 9%).

Workup

temperaturethe mixture was heated to 100° C. overnight
temperaturecooled
customthe organic layer was separated
extractionthe aqueous phase was extracted three times with EtOAc
concentrationThe combined organic phases were concentrated in vacuo
customthe residue was purified by flash silica chromatography
washeluting with a gradient of 0-20% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-46237b6a311b49d1a0b3ecfa6fc3402f
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728029B2

Reaction notes

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