Water → 4-(2,3,4,5,6-Pentafluorophenoxy)-4-phenylpiperidine

HRID 1031545

Reaction equation

HRID 1031545 reaction equation
[H-].[Na+].[OH:3][C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[F:16][C:17]1[C:22](F)=[C:21]([F:24])[C:20]([F:25])=[C:19]([F:26])[C:18]=1[F:27].O>CN(C)C=O>[F:16][C:17]1[C:18]([F:27])=[C:19]([F:26])[C:20]([F:25])=[C:21]([F:24])[C:22]=1[O:3][C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 9805HexafluorobenzeneHCID 24758Sodium hydrideHCID 963874-Phenylpiperidin-4-ol

Product 1

HCID 146499784-(2,3,4,5,6-Pentafluorophenoxy)-4-phenylpiperidineYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
50 °C

Procedure

To a suspension of sodium hydride (60% in oil, 6.4 g) in 50 ml of dry dimethylformamide was added, over a period of ten minutes, a solution of 25 g of 4-hydroxy-4-phenylpiperidine in 100 ml of dry dimethylformamide. After stirring at 50° C., for thirty minutes, the reaction mixture was cooled to ice bath temperature (5° C.). A solution of 18.6 ml of hexafluorobenzene in 100 ml of dry dimethylformamide was then added over a period of thirty minutes, and the resulting mixture stirred at ambient temperature for twenty hours. The mixture was poured into 500 ml water, stirred for five minutes, and extracted with ethyl acetate. The organic layer was washed with water followed by a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering, evaporation of the solvents afforded a residue which was purified by means of high pressure liquid chromatography (silica gel; elution with 20% methanol/dichloromethane) to afford 21 g (44%) of 4-(2,3,4,5,6-pentafluorophenoxy)-4-phenylpiperidine as an oil.

Workup

  1. additionwas added, over a period of ten minutes
  2. temperaturethe reaction mixture was cooled to ice bath temperature (5° C.)
  3. stirringthe resulting mixture stirred at ambient temperature for twenty hours
  4. stirringstirred for five minutes
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationAfter filtering
  9. customevaporation of the solvents
  10. customafforded a residue which
  11. customwas purified by means of high pressure liquid chromatography (silica gel; elution with 20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-328e9c6847e348d78475cd9183d1ee0d
Source dataset
uspto-grants-1990_09
Patent number
US04954511

Linked notes

Loading…