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

HRID 2087214Notes

Reaction equation

HRID 2087214 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-5781d110bd0b4fe3876cac16627af0cd
Source dataset
uspto-grants-2004_04
Patent number
US06727264B1

Reaction notes

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