Fluorobenzene → HCID 20306012, compound

HRID 1732337Notes

Reaction equation

HRID 1732337 reaction equation
C([N:4]1[CH2:9][CH2:8][CH:7]([O:10][CH2:11][CH:12]([OH:14])[CH3:13])[CH2:6][CH2:5]1)(=O)C.[H-].[Na+].F[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(O)(C)C>[O:14]([CH:12]([CH3:13])[CH2:11][O:10][CH:7]1[CH2:6][CH2:5][NH:4][CH2:9][CH2:8]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 10008FluorobenzeneHCID 24758Sodium hydrideHCID 20306035HCID 20306035, compound

Product 1

HCID 20306012HCID 20306012, compoundYield 3.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-Acetyl-4-(2-hydroxy-n-propoxy)piperidine (12 g.) in dry D.M.F. (50 ml.) was added dropwise to a stirred suspension of sodium hydride (5.0 g., 50% dispersion in mineral oil) in D.M.F. (50 ml.) at 60°-70° C. under an atmosphere of nitrogen. The suspension was stirred for 3 hours, then fluorobenzene (6.4 g.) in D.M.F. (50 ml.) added dropwise and the suspension stirred at 100° C. for 50 hours. The cooled solution was treated with isopropanol (20 ml.) then water (200 ml.), extracted with petroleum ether (3×200 ml.) and chloroform (3×200 ml.). The combined chloroform extracts were dried (Na2SO4) and the solvent evaporated in vacuo. The residue (9.0 g.) in sodium hydroxide solution (20 ml., 5N) and methanol (20 ml.) to bring about solution was heated under reflux for 5 hours. The methanol was evaporated, the residue diluted with water then extracted with chloroform (3×50 ml.). The combined chloroform extracts were washed with 2N HCl (3×30 ml.), the combined aqueous extracts basified to pH 12 with sodium hydroxide solution and extracted with chloroform (3×50 ml.). The combined chloroform layers were dried (Na2SO4), solvent evaporated in vacuo, then the residue triturated with ether and filtered. The filtrate was concentrated then distilled to give 4-(2-phenoxy-n-propoxy)piperidine (0.5 g.), b.p. 118°-122° C./0.3 mm., characterized spectroscopically.

Workup

  1. customat 60°-70° C.
  2. addition(50 ml.) added dropwise
  3. stirringthe suspension stirred at 100° C. for 50 hours
  4. extractionwater (200 ml.), extracted with petroleum ether (3×200 ml.) and chloroform (3×200 ml.)
  5. dry with materialThe combined chloroform extracts were dried (Na2SO4)
  6. customthe solvent evaporated in vacuo
  7. temperaturewas heated
  8. temperatureunder reflux for 5 hours
  9. customThe methanol was evaporated
  10. additionthe residue diluted with water
  11. extractionthen extracted with chloroform (3×50 ml.)
  12. washThe combined chloroform extracts were washed with 2N HCl (3×30 ml.)
  13. extractionextracted with chloroform (3×50 ml.)
  14. dry with materialThe combined chloroform layers were dried (Na2SO4), solvent
  15. customevaporated in vacuo
  16. customthe residue triturated with ether
  17. filtrationfiltered
  18. concentrationThe filtrate was concentrated
  19. distillationthen distilled

Sources & evidence

ORD record
ord-76b8dbe87a7a425fa48341dbb72b7bac
Source dataset
uspto-grants-1980_12
Patent number
US04237138

Reaction notes

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