Lithium hydroxide, monohydrate → 5-Methyl-3-pyridin-4-yl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid

HRID 1011961Notes

Reaction equation

C([O:3][C:4]([C:6]1[C:7]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)=[N:8][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:22])([F:21])[F:20])[CH:13]=2)[C:10]=1[CH3:11])=[O:5])C.O.[OH-].[Li+]>C1COCC1.CO.O.CCOC(C)=O>[CH3:11][C:10]1[N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:21])([F:20])[F:22])[CH:13]=2)[N:8]=[C:7]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[C:6]=1[C:4]([OH:5])=[O:3]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-methyl-3-pyridin-4-yl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester (605 mg, 1.55 mmol) in 5 ml THF, 2.5 ml methanol and 2.5 ml water, was added lithium hydroxide monohydrate (111 mg, 4.63 mmol). The solution was heated at 80° C. for 2 h. The reaction mixture was cooled, diluted with EtOAc and washed twice with 10% KHSO4 and brine. The aqueous phases were extracted with EtOAc and with three portions of CH2Cl2. The combined organic layers were dried over magnesium sulfate, and evaporated. The residue was precipitated from tBuOMe to give a white solid (436 mg, 76%) of the title compound. MS: 364.1 (MH+).

Workup

temperatureThe reaction mixture was cooled
washwashed twice with 10% KHSO4 and brine
extractionThe aqueous phases were extracted with EtOAc and with three portions of CH2Cl2
dry with materialThe combined organic layers were dried over magnesium sulfate
customevaporated
customThe residue was precipitated from tBuOMe

Sources & evidence

ORD record: ord-8695e4155af54e02ab0e743184839b9a
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977358B2

Reaction notes

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