Trifluoroacetic acid → 4-[4-(Trifluoromethoxy)phenoxy]piperidine

HRID 856102Notes

Reaction equation

HRID 856102 reaction equation
[F:1][C:2]([F:25])([F:24])[O:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[F:25][C:2]([F:1])([F:24])[O:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 23081100tert-Butyl 4-[4-(trifluoromethoxy)phenoxy]piperidine-1-carboxylate

Product 1

HCID 161154394-[4-(Trifluoromethoxy)phenoxy]piperidineYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-(4-trifluoromethoxyphenoxy)-piperidine-1-carboxylate (92 g, 254.59 mmol) prepared in Reference Example 189 was dissolved in methylene chloride (100 ml). Trifluoroacetic acid (200 ml) was added dropwise to this solution at room temperature, and the mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure, and the residue was then dissolved in methylene chloride, which was neutralized with a sodium hydroxide aqueous solution. The mixture was extracted with methylene chloride. The extract was washed with brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was then purified by silica gel column chromatography (methylene chloride/methanol=5/1) to afford 4-(4-trifluoromethoxyphenoxy)piperidine (55 g, yield 83%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was then dissolved in methylene chloride
  3. extractionThe mixture was extracted with methylene chloride
  4. washThe extract was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was then purified by silica gel column chromatography (methylene chloride/methanol=5/1)

Sources & evidence

ORD record
ord-48601dc8f2c84b50a540aafde8d76560
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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