Dimethylformamide → 2-Chloro-4-fluoro-5-[4-formyl-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzoic acid, 1-methylethyl ester

HRID 1379818Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([C:12]2[C:16]([CH:17]=[O:18])=[C:15]([C:19]([F:22])([F:21])[F:20])[N:14]([CH3:23])[N:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:24](Cl)(=O)[C:25](Cl)=O.[CH3:30]N(C=O)C>C(Cl)Cl.CC(O)C>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([C:12]2[C:16]([CH:17]=[O:18])=[C:15]([C:19]([F:20])([F:21])[F:22])[N:14]([CH3:23])[N:13]=2)=[CH:7][C:3]=1[C:4]([O:6][CH:24]([CH3:25])[CH3:30])=[O:5]

Participants

Conditions

Temperature: 50 °C

Procedure

To a slurry of 2.5 g of 2-chloro-4-fluoro-5-[4-formyl-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzoic acid (Ex. 3) in 50 ml of methylene chloride was added 10 mL of oxalyl chloride followed by catalytic DMF. The solution was stirred for one hour and concd in vacuo. The resultant residue was diluted in 2-propanol and heated to 50° C. for one hour. The reaction was poured onto water and extracted into diethyl ether. The combined organic extracts were washed with brine and 2.5N sodium hydroxide solution, dried and concd to give a material which contained the desired product and a bi-product. Chromatographic purification (silica, 10% ethyl acetate in hexanes) afforded 1.0 g of 2-chloro-4-fluoro-5-[4-formyl-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzoic acid, 1-methylethyl ester in a 36% yield: mp 90° C.; 1HNMR (CDCl3) δ 10.04 (s, 1H), 7.9 (d, 1H, J=7.6), 7.25 (d, 1H, J=9.2), 5.23 (m, 1H), 4.11 (s, 3H), 1.35 (d, 6H, J=6.0).

Workup

additionThe reaction was poured onto water
extractionextracted into diethyl ether
washThe combined organic extracts were washed with brine and 2.5N sodium hydroxide solution
customdried
customto give a material which

Sources & evidence

ORD record: ord-01eb3c2b315c4ad580684d5eebe3c08a
Source dataset: uspto-grants-1997_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05672715

Reaction notes

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