Trifluoroacetic acid → 4-(3-Fluorophenoxy)piperidine

HRID 906348Notes

Reaction equation

HRID 906348 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57699520Tert-butyl 4-(3-fluorophenoxy)piperidine-1-carboxylate

Product 1

HCID 185240024-(3-Fluorophenoxy)piperidineYield 111.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 4-[(3-fluorophenyl)oxy]-1-piperidinecarboxylate (D11) (16.4 g, 55 mmol) in DCM (200 ml) at 0° C. was treated with TFA (17 ml). The reaction was warmed to room temperature and stirred overnight. The solvent was then removed in vacuo and the residue partitioned between DCM and 2M NaOH solution. The aqueous was further extracted with DCM (×2) and the combined organics concentrated in vacuo. The residue was re-dissolved in DCM and extracted with 2M HCl (×2) which was then basified with 2M NaOH and re-extracted with DCM (×3). The combined organics were concentrated in vacuo to give the title compound (12 g). δH (CDCl3, 250 MHz) 1.66 (2H, m), 2.01 (2H, m), 2.73 (2H, m), 3.14 (2H, m), 4.34 (1H, m), 6.68 (3H, m), 7.19 (1H, m), MS (ES): MH+ 196. This whole was diluted with MeOH and treated with 1M HCl in Et2O to give the hydrochloride salt of the title compound (8.0 g).

Workup

  1. customThe solvent was then removed in vacuo
  2. customthe residue partitioned between DCM and 2M NaOH solution
  3. extractionThe aqueous was further extracted with DCM (×2)
  4. concentrationthe combined organics concentrated in vacuo
  5. dissolutionThe residue was re-dissolved in DCM
  6. extractionextracted with 2M HCl (×2) which
  7. extractionre-extracted with DCM (×3)
  8. concentrationThe combined organics were concentrated in vacuo

Sources & evidence

ORD record
ord-a2881ee2bc494afc87a53d881073b817
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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