3-Chloro-5-(trifluoromethyl)pyridin-2-ol → 3-chloro-1-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-5-trifluoromethyl-1H-pyridin-2-one

HRID 2106020Notes

Reaction equation

HRID 2106020 reaction equation
[Cl:1][C:2]1[C:3]([OH:12])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[O-]CC.[Na+].[F:17][C:18]1[CH:19]=[CH:20][C:21]([O:35][CH3:36])=[C:22]([C:24]([CH3:34])([CH3:33])[CH2:25][C:26]2([C:29]([F:32])([F:31])[F:30])[CH2:28][O:27]2)[CH:23]=1>CCO>[Cl:1][C:2]1[C:3](=[O:12])[N:4]([CH2:28][C:26]([OH:27])([C:29]([F:30])([F:32])[F:31])[CH2:25][C:24]([C:22]2[CH:23]=[C:18]([F:17])[CH:19]=[CH:20][C:21]=2[O:35][CH3:36])([CH3:33])[CH3:34])[CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

5

Reactant 3

HCID 7254363-Chloro-5-(trifluoromethyl)pyridin-2-olHCID 2723922Sodium ethoxideHCID 160992392-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxirane

Product 1

HCID 578098453-chloro-1-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-5-trifluoromethyl-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
85 °C

Procedure

A mixture of 3-chloro-5-trifluoromethylpyridin-2-ol (135 mg, 0.68 mmol) in 1 mL of EtOH was added to 0.13 mL of a 1M sodium ethoxide solution in ethanol and was heated to 85° C. for 5 minutes in a sealed vial. The mixture was cooled to room temperature, 2-[2-(5-fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxirane was added, and the mixture heated to 85° C. overnight in a sealed vial. The volatiles were removed in vacuo and the residue diluted with water and extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate and concentrated in vacuo. The residue was purified on PLC plate (hexanes-EtOAc (8:2)) to give 125 mg of 3-chloro-1-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-5-trifluoromethyl-1H-pyridin-2-one as a solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. temperaturethe mixture heated to 85° C. overnight in a sealed vial
  3. customThe volatiles were removed in vacuo
  4. additionthe residue diluted with water
  5. extractionextracted with EtOAc
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on PLC plate (hexanes-EtOAc (8:2))

Sources & evidence

ORD record
ord-2828e90cb9e0497c820579193ae2279a
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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