Sodium Hydroxide → [2-Methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-pyridin-3-yl]-methanol

HRID 890479Notes

Reaction equation

HRID 890479 reaction equation
C([O:3][C:4](=O)[C:5]1[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][C:8]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)=[N:7][C:6]=1[CH3:26])C.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>C(OCC)C>[CH3:26][C:6]1[C:5]([CH2:4][OH:3])=[C:10]([C:11]([F:14])([F:13])[F:12])[CH:9]=[C:8]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:24])([F:23])[F:25])=[CH:17][CH:16]=2)[N:7]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 76852879HCID 76852879, compound

Product 1

HCID 21935754[2-Methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-pyridin-3-yl]-methanolYield 40%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-nicotinic acid ethyl ester (400 mg, 1 mmol) in diethyl ether (6 ml) was added to a suspension of lithium aluminium hydride (77 mg, 2 mmol) in diethyl ether (12 ml) under an argon atmosphere at ambient temperature within 5 min. The mixture was stirred at reflux for 12 h, cooled to 0° C. and treated cautiously with ice water (12 ml) and 10% aqueous NaOH (6 ml). The reaction mixture was filtered over celite, t-butyl methylether was added and the layers were separated. The aqueous layer was extracted one more time with t-butyl methylether, the combined organic layers were washed with ice water/brine 1/1 and dried over sodium sulfate. Removal of the solvent under reduced pressure gave an orange oil which was purified by column chromatography (silica gel, heptane/AcOEt) to yield 140 mg (400 μmol, 39%) of the title compound as colorless crystals.

Workup

  1. temperatureat reflux for 12 h
  2. filtrationThe reaction mixture was filtered over celite, t-butyl methylether
  3. additionwas added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted one more time with t-butyl methylether
  6. washthe combined organic layers were washed with ice water/brine 1/1
  7. dry with materialdried over sodium sulfate
  8. customRemoval of the solvent under reduced pressure
  9. customgave an orange oil which
  10. customwas purified by column chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-64a17f1b3e354709b7605d0df73e6f40
Source dataset
uspto-grants-2006_02
Patent number
US06995263B2

Reaction notes

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