Sulfuric Acid → 1-Benzhydryl-3-ethylaminoazetidine-3-carboxylic Acid Amide

HRID 1246797Notes

Reaction equation

HRID 1246797 reaction equation
[CH:1]([N:14]1[CH2:17][C:16]([NH:20][CH2:21][CH3:22])([C:18]#[N:19])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:23]S(O)(=O)=O>C(Cl)Cl.C(OCC)(=O)C>[CH:1]([N:14]1[CH2:17][C:16]([NH:20][CH2:21][CH3:22])([C:18]([NH2:19])=[O:23])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 219058181-Benzhydryl-3-ethylaminoazetidine-3-carbonitrile

Product 1

HCID 587217631-Benzhydryl-3-ethylaminoazetidine-3-carboxylic Acid Amide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A vigorously stirred solution of 1-benzhydryl-3-ethylaminoazetidine-3-carbonitrile (I-(13A-9)d; 11.7 g, 40 mmol) in methylene chloride (150 ml) cooled in an ice bath was treated with H2SO4 (22 ml, 0.4 mol), dropwise. After the reaction mixture was allowed to warm to room temperature and stir overnight, it was cooled in an ice bath and then carefully quenched with concentrated NH4OH to pH 11. The off-white solids that formed during the quench were collected by vacuum filtration. The aqueous mixture was then extracted with methylene chloride, the combined organic layers were washed with brine, dried (Na2SO4) and then concentrated, in vacuo, to afford additional solids. The combined solids were stirred for 1 hour in ethyl acetate (150 mL) and then collected by vacuum filtration to give I-(13A-9)e (9.2 g, 74%) as a solid: +ES MS (M+1) 310.2; 1H NMR (400 MHz, CD3OD) δ 7.41 (d, J=7.1 Hz, 4H), 7.25 (t, J=7.5 Hz, 4H), 7.16 (t, J=7.5 Hz, 2H), 4.49 (s, 1H), 3.44 (d, J=8.3 Hz, 2H), 3.11 (d, J=8.3 Hz, 2H), 2.47 (q, J=7.1 Hz, 2H), 1.10 (t, J=7.3 Hz, 3H).

Workup

  1. temperatureit was cooled in an ice bath
  2. customcarefully quenched with concentrated NH4OH to pH 11
  3. customThe off-white solids that formed during the quench
  4. filtrationwere collected by vacuum filtration
  5. extractionThe aqueous mixture was then extracted with methylene chloride
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated, in vacuo
  9. customto afford additional solids
  10. filtrationcollected by vacuum filtration
  11. customto give I-(13A-9)e (9.2 g, 74%) as a solid

Sources & evidence

ORD record
ord-43711c43830d4b90a2cb292719c4a29b
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

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