p-Aminoacetophenone → N-[4-(1-hydroxyiminoethyl)phenyl]-N'-bis(methoxycarbonyl)methylurea

HRID 247226Notes

Reaction equation

HRID 247226 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][CH:5]=1)=O.[N:11]([CH:14]([C:19]([O:21][CH3:22])=[O:20])[C:15]([O:17][CH3:18])=[O:16])=[C:12]=[O:13].Cl.[NH2:24][OH:25].C(OC)(OC)OC>C1COCC1.N1C=CC=CC=1>[OH:25][N:24]=[C:2]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:12]([NH:11][CH:14]([C:19]([O:21][CH3:22])=[O:20])[C:15]([O:17][CH3:18])=[O:16])=[O:13])=[CH:6][CH:5]=1)[CH3:1]

Participants

7

Reactant 4

HCID 7468p-AminoacetophenoneHCID 9005Trimethyl orthoformateHCID 443297Hydroxyamine hydrochlorideHCID 14876291Dimethyl isocyanatomalonate

Product 1

HCID 86741886N-[4-(1-hydroxyiminoethyl)phenyl]-N'-bis(methoxycarbonyl)methylurea

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.02 mol 4-aminoacetophenone in 40 mL THF if added dropwise to a solution of 0.02 mol of dimethyl isocyanatomalonate and 5 mL pyridine in 40 mL THF, and the reaction mixture is stirred for 3 hours. The solvent is then removed by rotary evaporator. The residue is dispersed in 50 mL CH3OH, and 0.022 hydroxylamine hydrochloride and 0.06 mol trimethyl orthoformate are added. The reaction mixture is heated to reflux for 10 hours. The solvent is removed by rotary evaporator. Addition of water to the residue results in formation of N-[4-(1-hydroxyiminoethyl)phenyl]-N'-bis(methoxycarbonyl)methylurea, which is then treated with NaOCH3 to adjust the pH to 10. The solution is heated to reflux for 2.5 hours, and the solvent is removed under vacuum. The residue is washed with cold water to yield the crude 3-[4-(1-hydroxyiminoethyl)phenyl]-5-methoxycarbonylhydantoin.

Workup

  1. customThe solvent is then removed by rotary evaporator
  2. additionThe residue is dispersed in 50 mL CH3OH
  3. temperatureThe reaction mixture is heated
  4. temperatureto reflux for 10 hours
  5. customThe solvent is removed by rotary evaporator
  6. additionAddition of water to the residue

Sources & evidence

ORD record
ord-adcab2c90b9d4fa39e7676b8a03f3d0f
Source dataset
uspto-grants-1987_11
Patent number
US04705864

Reaction notes

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