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

HRID 2054386Notes

Reaction equation

HRID 2054386 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 I-1A-1f (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 hours. 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 the 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-1A-1q as a pale orange oil that solidified 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 the 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-1A-1q as a pale orange oil that solidified to a peach

Sources & evidence

ORD record
ord-c42b16c16e164d23b7ae7b7db52c3172
Source dataset
uspto-grants-2008_02
Patent number
US07329658B2

Reaction notes

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