Hydrochloric Acid → 1-[4-(Trifluoromethoxy)phenyl]piperidin-4-one

HRID 856025Notes

Reaction equation

HRID 856025 reaction equation
[F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:19][CH2:18][C:13]3(OCC[O:14]3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.Cl.O>C(O)C>[F:21][C:2]([F:1])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:11][CH2:12][C:13](=[O:14])[CH2:18][CH2:19]2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 23081384HCID 23081384, compound

Product 1

HCID 230815881-[4-(Trifluoromethoxy)phenyl]piperidin-4-oneYield 81%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 8-(4-trifluoromethoxyphenyl)-1,4-dioxa-8-azaspiro[4.5]decane (1.23 g, 4.06 mmol) prepared in Reference Example 21, concentrated hydrochloric acid (5 ml), water (10 ml), and ethanol (30 ml) was heated under reflux for 5 hours. The reaction mixture was allowed to return to room temperature and concentrated under reduced pressure. To the residue, 10% sodium hydroxide aqueous solution was added, and the mixture was extracted with methylene chloride. The extract was washed with water and brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/1) to afford 1-(4-trifluoromethoxyphenyl)piperidin-4-one (848 mg, yield 81%) as a colorless oil.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 5 hours
  3. customto return to room temperature
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue, 10% sodium hydroxide aqueous solution was added
  6. extractionthe mixture was extracted with methylene chloride
  7. washThe extract was washed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationAfter filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-7d0ac2da7807467dad6a68208b380c31
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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