Sulfuric Acid → 1-Benzyl-4-(ethylamino)piperidine-4-carboxamide

HRID 1246789Notes

Reaction equation

HRID 1246789 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:16][CH2:17][CH3:18])([C:14]#[N:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:19]S(O)(=O)=O>C(Cl)Cl>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:16][CH2:17][CH3:18])([C:14]([NH2:15])=[O:19])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 705581-Benzyl-4-(ethylamino)piperidine-4-carbonitrile

Product 1

HCID 705671-Benzyl-4-(ethylamino)piperidine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-benzyl-4-ethylaminopiperidine-4-carbonitrile 1-(7A-80)d (0.58 g, 2.38 mmol) in methylene chloride (2 ml) cooled in an ice bath was treated with H2SO4 (1.8 ml, 33 mmol), dropwise, while keeping the internal temperature below 20° C. The reaction was then warmed to room temperature and stirred for 19 hr. After stirring was discontinued, the thick pale orange H2SO4 bottom layer was separated, cooled in an ice bath and then carefully quenched with concentrated NH4OH keeping internal temperature below 55° C. The aqueous layer was extracted with methylene chloride (2×10 ml), the combined organic layers were washed with brine (20 ml), dried (Na2SO4), and then concentrated in vacuo to afford I-(7A-80)e as a pale orange oil that solidifies to a peach colored solid upon standing (0.54 g, 87%): +APCI MS (M+1) 262.2; 1H NMR (400 MHz, CD2Cl2) δ 7.34–7.30 (m, 4H), 7.29–7.21 (m, 1H), 7.16 (br s, 1H), 3.48 (s, 2H), 2.71–2.68 (m, 2H), 2.47 (q, J=7.0 Hz, 2H), 2.17–2.02 (m, 4H), 1.62–1.58 (m, 2H), 1.41 (br s, 1H), 1.09 (t, J=7.0 Hz, 3H).

Workup

  1. customthe internal temperature below 20° C
  2. stirringAfter stirring
  3. customthe thick pale orange H2SO4 bottom layer was separated
  4. temperaturecooled in an ice bath
  5. customcarefully quenched with concentrated NH4OH keeping internal temperature below 55° C
  6. extractionThe aqueous layer was extracted with methylene chloride (2×10 ml)
  7. washthe combined organic layers were washed with brine (20 ml)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford I-(7A-80)e as a pale orange oil

Sources & evidence

ORD record
ord-1120943bd2454cd49694a1cff5939a64
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

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