Dimethylformamide → 4-[2-(4-Trifluoromethoxyphenoxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester

HRID 2172211Notes

Reaction equation

HRID 2172211 reaction equation
[H-].[Na+].CN(C)C=O.[F:8][C:9]([F:19])([F:18])[O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([CH2:33][CH2:34]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>O>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([CH2:33][CH2:34][O:17][C:14]2[CH:13]=[CH:12][C:11]([O:10][C:9]([F:18])([F:19])[F:8])=[CH:16][CH:15]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 70015p-(Trifluoromethoxy)phenolHCID 21936070N-Boc-4-[2-(4-Toluenesulfonyloxy)ethyl]piperidine

Product 1

HCID 708737904-[2-(4-Trifluoromethoxyphenoxy)ethyl]piperidine-1-carboxylic acid tert-butyl esterYield 103.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium hydride (60% in oil, 2.12 g) wad added to an N,N-dimethylformamide solution (100 ml) of 4-trifluoromethoxyphenol (9.0 g) under ice cooling and stirred for 30 minutes. After adding 4-[2-(toluene-4-sulfonyloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester (17.7 g), the mixture was heated to room temperature and stirred. The mixture was further stirred at 50° C. for 1 hour. After cooling the reaction mixture to room temperature, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over sodium sulfate. The result was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=67:33) to afford the title compound as a pale yellow oil (18.64 g).

Workup

  1. stirringstirred
  2. stirringThe mixture was further stirred at 50° C. for 1 hour
  3. temperatureAfter cooling the reaction mixture to room temperature
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  6. dry with materialdried over sodium sulfate
  7. concentrationThe result was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=67:33)

Sources & evidence

ORD record
ord-101ca1b167f547c18310f88a79708d9a
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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