Phenol → 3-[(4-Chlorophenyl)sulfanyl]piperidine--hydrogen chloride (1/1)

HRID 236092Notes

Reaction equation

HRID 236092 reaction equation
[Cl:1]C1C=CC(S)=CC=1.C(=O)([O-])[O-].[Na+].[Na+].S([N:25]1[CH2:30][CH2:29][CH2:28][CH:27]([S:31][C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[CH2:26]1)(C1C=CC(C)=CC=1)(=O)=O.C1(O)C=CC=CC=1>CN(C)C=O.Br>[ClH:1].[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([S:31][CH:27]2[CH2:28][CH2:29][CH2:30][NH:25][CH2:26]2)=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 996PhenolHCID 7815p-ChlorothiophenolHCID 10340Sodium CarbonateHCID 13607947HCID 13607947, compound

Product 1

HCID 177497783-[(4-Chlorophenyl)sulfanyl]piperidine--hydrogen chloride (1/1)

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 54 g (0.375 mole) of p-chlorothiophenol, 51.4 g (0.126 mole) of 1-[(4-methylphenyl)sulfonyl]-3-piperidinol-4-methylphenylsulfonate ester and 35 g of sodium carbonate in 500 ml of dimethylformamide was heated at 100° C. for 18 hr. The mixture was cooled and quenched in excess 1M sodium hydroxide solution. The aqueous mixture was extracted with several portions of methylene chloride and the combined methylene chloride extracts were extracted with several portions of 1M sodium hydroxide solution and dried over magnesium sulfate. The solvent was removed in vacuo to give an oil which was shown by NMR, mass spectrum and TLC to be impure N-tosyl-3-(p-chlorothiophenoxy)piperidine. (See Preparation 13 for the pure compound). A mixture of this compound and excess phenol in 75 ml of 48% hydrobromic acid was refluxed for 1 hr and quenched in an ice-water mix. The mixture was made basic with sodium hydroxide and was extracted with several portions of methylene chloride. The aqueous layer was discarded. The combined methylene chloride extracts were dried over magnesium sulfate and the methylene chloride was removed in vacuo to give an oil, the free base of the title compound. The free base was reacted with hydrogen chloride using the solvent pair diethyl ether-methanol for crystallization and recrystallization to obtain the white crystalline hydrochloride salt, m.p. 159°-161° C.

Workup

  1. temperatureThe mixture was cooled
  2. customquenched in excess 1M sodium hydroxide solution
  3. extractionThe aqueous mixture was extracted with several portions of methylene chloride
  4. extractionthe combined methylene chloride extracts were extracted with several portions of 1M sodium hydroxide solution
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was removed in vacuo
  7. customto give an oil which
  8. customPreparation 13 for the pure compound)
  9. temperaturewas refluxed for 1 hr
  10. customquenched in an ice-water
  11. additionmix
  12. extractionwas extracted with several portions of methylene chloride
  13. dry with materialThe combined methylene chloride extracts were dried over magnesium sulfate
  14. customthe methylene chloride was removed in vacuo
  15. customto give an oil

Sources & evidence

ORD record
ord-855f35ec19714bd5804e633269b120c0
Source dataset
uspto-grants-1987_02
Patent number
US04642348

Reaction notes

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