Hydrofluoric Acid → HCID 15469929, compound

HRID 1983676Notes

Reaction equation

HRID 1983676 reaction equation
[FH:1].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2(O)[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([F:1])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 14917Hydrofluoric AcidHCID 382824-(4-Chlorophenyl)-4-hydroxypiperidineHCID 516892Sodium Bicarbonate

Product 1

HCID 15469929HCID 15469929, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of hydrogen fluoride (65-70%) in pyridine (4 ml) was added 4-(4-chloro-phenyl)-piperidin-4-ol (500 mg, 2.36 mmol). The resulting solution was stirred at 0° C. for 15 min and then warmed to rt and stirred 1 h. The mixture was slowly poured into a saturated aqueous sodium bicarbonate solution (30 mL) and extracted with methylene chloride (100 ml; ADD SOLVENT AND EXTRACT SLOWLY AND WITH CAUTION). Excess hydrogen fluoride was neutralized with solid sodium carbonate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography, eluting with a methylene chloride to methylene chloride/methanol/ammonium hydroxide (8.5/1/0.5) gradient to give 4-(4-Chloro-phenyl)-4-fluoro-piperidine (260 mg, 52%).

Workup

  1. temperaturewarmed to rt
  2. stirringstirred 1 h
  3. extractionextracted with methylene chloride (100 ml
  4. extractionADD SOLVENT AND EXTRACT SLOWLY AND WITH CAUTION)
  5. washThe organic phase was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography
  10. washeluting with a methylene chloride to methylene chloride/methanol/ammonium hydroxide (8.5/1/0.5) gradient

Sources & evidence

ORD record
ord-65839ffb32a541fa9e47c360b62c51e9
Source dataset
uspto-grants-2009_06
Patent number
US07541365B2

Reaction notes

Loading…