Water → HCID 23149870, compound

HRID 1670770Notes

Reaction equation

HRID 1670770 reaction equation
C(OC([N:6]1[CH2:11][CH2:10][C:9]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([C:20]([F:23])([F:22])[F:21])[CH:14]=2)([OH:12])[CH2:8][CH2:7]1)=O)C.[H-].[Na+].[CH3:26]I.O>CN(C)C=O>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:9]2([O:12][CH3:26])[CH2:10][CH2:11][NH:6][CH2:7][CH2:8]2)=[CH:14][C:15]=1[C:20]([F:23])([F:22])[F:21]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 89106Ethyl 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 23149870HCID 23149870, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-[4-Chloro-3-(trifluoromethyl)phenyl]-4-hydroxy-1-piperidinecarboxylic acid ethyl ester (2.0 g) was dissolved in dimethylformamide and the mixture was cooled to 0° C. Sodium hydride (250 mg) was added thereto, and the mixture was stirred for 30 min. Then, methyl iodide (0.4 ml) was added, and the mixture was further stirred for 30 min and warmed to room temperature. Water was added thereto, and the mixture was extracted three times with methylene chloride. The organic layer dried over magnesium sulfate and the solvent was evaporated under reduced pressure. Ethanol (20 ml) and a 6N aqueous sodium hydroxide solution (15 ml) were added to the obtained residue, and the mixture was heated under reflux for hr. The reaction mixture was allowed to cool to room temperature, neutralized with 12N aqueous hydrochloric acid, and extracted three times with chloroform. The organic layer was dried and the solvent was evaporated under reduced pressure to give 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-methoxypiperidine (1.56 g, yield 93%).

Workup

  1. stirringthe mixture was further stirred for 30 min
  2. temperaturewarmed to room temperature
  3. extractionthe mixture was extracted three times with methylene chloride
  4. dry with materialThe organic layer dried over magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. additionEthanol (20 ml) and a 6N aqueous sodium hydroxide solution (15 ml) were added to the obtained residue
  7. temperaturethe mixture was heated
  8. temperatureunder reflux for hr
  9. temperatureto cool to room temperature
  10. extractionextracted three times with chloroform
  11. customThe organic layer was dried
  12. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-80ad47db60db45e8936aff56918286a9
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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