Hydrochloric Acid → HCID 20144933, compound

HRID 437568Notes

Reaction equation

HRID 437568 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[H][H].[F:19][C:20]1[CH:25]=[CH:24][C:23](F)=[CH:22][CH:21]=1.[ClH:27]>C(O)C.CN(C)C=O>[ClH:27].[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:23]2[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 108921,4-DifluorobenzeneHCID 24758Sodium hydrideHCID 784611-Benzylpiperidin-4-olHCID 178418361HCID 178418361, compound

Product 1

HCID 20144933HCID 20144933, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
80 °C

Procedure

86.4 g of 1-benzyl-4-piperidinol in 200 ml. and dimethylformamide are added dropwise to a stirred suspension of 34.7 g of a 50% oil dispersion of sodium hydride in 900 ml. of dimethylformamide at 60°-70° C. When no more hydrogen gas is liberated, a mixture of 68.4 g of p-difluorobenzene in 200 ml. of dimethylformamide is added slowly, and the temperature is raised to 80° C. Stirring and heating is continued for 48 hours, the reaction is cooled, poured into 2 l. of water, and the aqueous suspension is extracted with benzene. The benzene extracts are dried and the benzene is removed under reduced pressure, leaving a thick brown oil. The oil solidifies on standing. The solid is dissolved in 95% ethanol, the solution is filtered and the solvent is removed from the filtrate, leaving a yellow oil. The oil is dissolved in absolute ethanol, the solution is stirred, and saturated ethereal-HCl is added. A resultant hydrochloride salt precipitates out of solution and is collected and dried. The salt is recrystallized from an ethanol and ether mixture to give 1-benzyl-4-(p-fluorophenoxy)piperidine hydrochloride.

Workup

  1. customat 60°-70° C
  2. temperatureheating
  3. temperaturethe reaction is cooled
  4. additionpoured into 2 l
  5. extractionof water, and the aqueous suspension is extracted with benzene
  6. dry with materialThe benzene extracts are dried
  7. customthe benzene is removed under reduced pressure
  8. customleaving a thick brown oil
  9. filtrationthe solution is filtered
  10. customthe solvent is removed from the filtrate
  11. customleaving a yellow oil
  12. stirringthe solution is stirred
  13. customA resultant hydrochloride salt precipitates out of solution
  14. customis collected
  15. customdried
  16. customThe salt is recrystallized from an ethanol and ether mixture

Sources & evidence

ORD record
ord-b004b47472c84ea5af4ed9f799117897
Source dataset
uspto-grants-1977_06
Patent number
US04031221

Reaction notes

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