Diethyl (ethoxymethylene)malonate → Ethyl 4-hydroxy-2-phenylpyrimidine-5-carboxylate

HRID 842053Notes

Reaction equation

HRID 842053 reaction equation
C[O-].[Na+].Cl.[C:5]([NH2:13])(=[NH:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C([O:16][CH:17]=[C:18]([C:24](OCC)=O)[C:19]([O:21][CH2:22][CH3:23])=[O:20])C>C(O)C>[O:16]=[C:17]1[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:24][N:13]=[C:5]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[NH:12]1

Participants

5

Reactant 3

HCID 6871Diethyl (ethoxymethylene)malonateHCID 80289Benzamidine, hydrochlorideHCID 10942334Sodium Methoxide

Product 1

HCID 657593Ethyl 4-hydroxy-2-phenylpyrimidine-5-carboxylateYield 77.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of sodium methoxide (16.5 g) and anhydrous ethanol (200 ml) is added benzamidine hydrochloride (16 g) at 0-5° C. The mixture is stirred at 0° C. for 30 minutes, and thereto is added dropwise a solution of diethyl ethoxymethylenemalonate (20 g) in anhydrous ethanol (50 ml) at the same temperature. After the addition, the mixture is stirred at room temperature for 30 minutes, and refluxed for 6 hours. The reaction mixture is concentrated under reduced pressure, and the residue is dissolved in water. To the mixture is added with stirring and drowpise hydrochloric acid at 0-5° C. until the pH value of the mixture is adjusted to pH 4. The precipitates are collected by filtration, washed with water, washed with diethyl ether, and washed with ethanol to give the desired compound (17.5 g).

Workup

  1. additionAfter the addition
  2. stirringthe mixture is stirred at room temperature for 30 minutes
  3. temperaturerefluxed for 6 hours
  4. concentrationThe reaction mixture is concentrated under reduced pressure
  5. dissolutionthe residue is dissolved in water
  6. additionTo the mixture is added
  7. stirringwith stirring
  8. customat 0-5° C.
  9. filtrationThe precipitates are collected by filtration
  10. washwashed with water
  11. washwashed with diethyl ether
  12. washwashed with ethanol

Sources & evidence

ORD record
ord-cb2b21fcbfb8465ebb4b51a824777821
Source dataset
uspto-grants-2002_04
Patent number
US06372740B1

Reaction notes

Loading…