Hydrochloric Acid → N-[3-(4-Piperidinyl)phenyl]propanamide

HRID 1832221Notes

Reaction equation

HRID 1832221 reaction equation
[C:1]([NH:5][C:6]1[CH:7]=[C:8]([CH:12]2[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH:9]=[CH:10][CH:11]=1)(=[O:4])[CH2:2][CH3:3].Cl>O1CCOCC1>[NH:15]1[CH2:16][CH2:17][CH:12]([C:8]2[CH:7]=[C:6]([NH:5][C:1](=[O:4])[CH2:2][CH3:3])[CH:11]=[CH:10][CH:9]=2)[CH2:13][CH2:14]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 22049473Tert-butyl 4-[3-(propionylamino)phenyl]-1-piperidinecarboxylate

Product 1

HCID 22048836N-[3-(4-Piperidinyl)phenyl]propanamideYield 99,880.703%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Into a stirred solution of tert-butyl 4-[3-(propionylamino)phenyl]-1-piperidinecarboxylate (18.8 g, 0.0543 mmol) in dioxane (100 mL) at 5° C. was bubbled HCl gas for 2 h. The solvent was removed in vacuo, the residue was dissolved in water (100 mL) and neutralized by adding 10% KOH aqueous solution. The aqueous layer was extracted (3×200 mL) with a mixture of CHCl3/isopropyl alcohol (3:1), and the combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2 to afford the desired product (12.6 g, 99%). 1H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.32 (d, 1H, J=7.2 Hz), 7.28–7.21 (m, 1H), 7.09 (s, 1H), 6.97 (d, 1H, J=7.6 Hz), 3.18 (d, 2H, J=12.6 Hz), 2.73 (dt, 2H, J=2.2, 11.2 Hz), 2.65–2.57 (m, 1H), 2.38 (q, 2H, J=7.4 Hz), 1.83 (d, 2H, J=12.1 Hz), 1.70–1.61 (m, 3H), 1.25 (t, 3H, J=7.5 Hz); ESMS m/e: 233.1 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in water (100 mL)
  3. additionby adding 10% KOH aqueous solution
  4. extractionThe aqueous layer was extracted (3×200 mL)
  5. additionwith a mixture of CHCl3/isopropyl alcohol (3:1)
  6. washthe combined organic layers were washed with brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2

Sources & evidence

ORD record
ord-70fe16b37961470190e0fed71b4553b3
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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