Lithium Hydroxide → 2-Methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acid
Reaction equation
C[O:2][C:3](=[O:23])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)=[N:6][C:5]=1[O:21][CH3:22].[OH-].[Li+].Cl.O>C1COCC1.CO>[CH3:22][O:21][C:5]1[N:6]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:18])[F:19])[CH:12]=2)[CH:8]=[C:9]([CH3:10])[C:4]=1[C:3]([OH:23])=[O:2]Participants
5
Procedure
To a solution of 0.325 g (1.00 mmol) of 2-methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acid methyl ester (intermediate 5C) in 20 ml of THF/MeOH (1:1) was added 2.50 ml (2.50 mmol) of lithium hydroxide solution (1 molar in water) drop by drop and the reaction mixture was then heated up to reflux. After 8 hours, it was poured into crashed ice and acidified with HCl/H2O (1N) to pH 3.0 and then extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1) to give 0.24 g (77%) of the title compound as light yellow solid. MS: 310.0 (M−H−).
Workup
- temperaturethe reaction mixture was then heated up
- temperatureto reflux
- additionit was poured
- extractionextracted twice with EtOAc
- washthe organic phases were washed with water
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- customevaporated
- customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1)
Sources & evidence
- ORD record
- ord-2c73d2bf00ce45a3b63a7792bae5cf7b
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08227613B2
Reaction notes
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