Hexane → Methyl 2-chloro-4-(3-Methyl-1H-pyrazol-1-yl)benzoate

HRID 1978198Notes

Reaction equation

CCCCCC.[H-].[K+].[CH3:9][C:10]1[CH:14]=[CH:13][NH:12][N:11]=1.[CH3:15][O:16][C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21](F)=[CH:20][C:19]=1[Cl:25]>CN(C)C=O>[CH3:15][O:16][C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([N:12]2[CH:13]=[CH:14][C:10]([CH3:9])=[N:11]2)=[CH:20][C:19]=1[Cl:25]

Participants

Conditions

Temperature: 130 °C

Procedure

Under anhydrous conditions a stirred suspension of hexane washed potassium hydride (0.424 g, 10.6 mmol) in 5 mL of dimethylformamide was treated in one portion with 3-methyl pyrazole (0.85 mL, 10.6 mmol). After the gas evolution ceased, 2-chloro-4-fluorobenzoic acid methyl ester (2.0 g, 10.6 mmol) was added to the clear solution. The mixture was heated at 130° C. for 15 minutes, cooled, and partitioned between ethyl acetate and brine. The organic layer was washed with water and brine, and dried over sodium sulfate. Removal of solvent afforded 2.2 g of a yellow oil consisting of a mixture of 3-methyl and 5-methylpyrazole regioisomers. In addition, about 20% of the acid derived from hydrolysis of the ester was detected by analysis of the NMR spectrum of the crude product. The desired 3-methylpyrazole regioisomer was separated from the 5-methyl isomer of Example 16 by flash chromatography (on silica Merck-60, dichloromethane-hexane 2:1) and was isolated as a white solid (1.55 g).

Workup

temperaturecooled
custompartitioned between ethyl acetate and brine
washThe organic layer was washed with water and brine
dry with materialdried over sodium sulfate
customRemoval of solvent

Sources & evidence

ORD record: ord-4311fe8804a24d40975f0969f19424a9
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06235900B1

Reaction notes

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