Hydrochloric Acid → N-{2-[3-(1-Methylpiperidin-2-yl)propyl]phenyl}-3-phenylprop-2-enamide

HRID 1659239Notes

Reaction equation

HRID 1659239 reaction equation
CO[C:3]1[CH:27]=[CH:26][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][N:20]2[CH3:25])=[O:8])=[CH:5][CH:4]=1.Cl.[OH-].[Na+].N[C:32]1C=CC=C[C:33]=1CCCC1CCCCN1C.C(Cl)(=O)C=CC1C=CC=CC=1>O.N1C=CC=CC=1.C1COCC1>[CH3:25][N:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH:19]1[CH2:18][CH2:17][CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:7](=[O:8])[CH:6]=[CH:5][C:4]1[CH:3]=[CH:27][CH:26]=[CH:33][CH:32]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 660233-Phenylprop-2-enoyl chlorideHCID 205599504-Methoxy-N-{2-[3-(1-methylpiperidin-2-yl)propyl]phenyl}benzamideHCID 53764394HCID 53764394, compound

Product 1

HCID 53946135N-{2-[3-(1-Methylpiperidin-2-yl)propyl]phenyl}-3-phenylprop-2-enamideYield 46%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-methoxy-2'-[3-(1-methyl-2-piperidyl)propyl]benzanilide (3.5 g., 0.0095 mole) and concentrated HCl (50 ml.) is heated at reflux for 16 hr., diluted with H2O (100 ml.), basified with 50% NaOH, and extracted with Et2O. The Et2O extracts are combined, washed (H2O and saturated NaCl), dried over MgSO4, and concentrated to give 2.2 g. of 2-(o-aminophenylpropyl)-1-methylpiperidine. The amine is dissolved in pyridine (50 ml.) and a solution of cinnamoyl chloride (1.8 g., 0.011 mole) in THF (10 ml.) added. The reaction mixture is stirred for 3 hr., then concentrated to dryness. The residue is dissolved in water, basified with 50% NaOH, and extracted with EtOAc. The EtOAc extracts are washed (H2O+saturated NaCl), dried over magnesium sulfate, and concentrated to give 3.4 g. of oil which is chromatographed on silica AR CC-7 (Mallinckrodt). Elution first with CHCl3 to remove impurities, then with EtOAc to remove the product and concentration of the EtOAc eluate gave 2.3 g. of solid which crystallized from EtOAc yields 1.6 g (46%) of 2'-[3-(1-methyl-2-piperidyl)propyl]cinnamanilide, m.p. 130°-132° C. Further crystallization from ethyl acetateisopropyl ether provides analytically pure product, m.p. 133.5°-134.5° C.

Workup

  1. temperatureat reflux for 16 hr
  2. extractionextracted with Et2O
  3. washwashed (H2O and saturated NaCl)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give 2.2 g
  7. concentration, then concentrated to dryness
  8. dissolutionThe residue is dissolved in water
  9. extractionextracted with EtOAc
  10. washThe EtOAc extracts are washed (H2O+saturated NaCl)
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated
  13. customto give 3.4 g
  14. customof oil which is chromatographed on silica AR CC-7 (Mallinckrodt)
  15. washElution first with CHCl3
  16. customto remove impurities
  17. customwith EtOAc to remove the product and concentration of the EtOAc eluate
  18. customgave 2.3 g
  19. customof solid which crystallized from EtOAc

Sources & evidence

ORD record
ord-bda49ae2c89a4d5ca42a9aeb474dde90
Source dataset
uspto-grants-1981_12
Patent number
USRE030811

Reaction notes

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