Lithium Hydroxide → 2-Methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acid

HRID 1692390Notes

Reaction equation

HRID 1692390 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

Reactant 3

HCID 3939Lithium HydroxideHCID 21885828Hydrate;hydrochlorideHCID 57441128HCID 57441128, compound

Product 1

HCID 574411372-Methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acidYield 77.1%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 0.325 g (1.00 mmol) of 2-methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acid methyl ester 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

  1. temperaturethe reaction mixture was then heated up
  2. temperatureto reflux
  3. additionit was poured
  4. extractionextracted twice with EtOAc
  5. washthe organic phases were washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1)

Sources & evidence

ORD record
ord-7757efeda4534b71866da52c8446d5d9
Source dataset
uspto-grants-2012_04
Patent number
US08153805B2

Reaction notes

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