Potassium Carbonate → 4-carboxy-2-cyclopropylmethyl-6-(2,3-dihydro-1-benzofuran-5-yl)-2H-pyridazin-3-one

HRID 2249408Notes

Reaction equation

HRID 2249408 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:11]=[C:12]([C:17]([O:19]C)=[O:18])[C:13](=[O:16])[NH:14][N:15]=3)=[CH:9][C:4]=2[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][CH:29]1[CH2:31][CH2:30]1.C(=O)([O-])O.[Na+]>CN(C)C=O>[C:17]([C:12]1[C:13](=[O:16])[N:14]([CH2:28][CH:29]2[CH2:31][CH2:30]2)[N:15]=[C:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][CH2:3][C:4]=3[CH:9]=2)[CH:11]=1)([OH:19])=[O:18]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 516892Sodium BicarbonateHCID 23094117HCID 23094117, compound

Product 1

HCID 230941314-carboxy-2-cyclopropylmethyl-6-(2,3-dihydro-1-benzofuran-5-yl)-2H-pyridazin-3-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

6-(2,3-Dihydro-1-benzofuran-5-yl)-4-methoxycarbonyl-2H-pyridazin-3-one (2.0 g, 7.35 mmol) was dissolved in N,N-dimethylformamide (17 mL), and potassium carbonate (2.0 g, 14.7 mmol) and bromomethylcyclopropane (1.2 g, 8.8 mmol) were added to the resultant solution, followed by stirring for two hours at 80° C. The temperature of the reaction mixture was reduced to room temperature, and saturated aqueous sodium hydrogencarbonate solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate anhydrate, and the solvent was removed through distillation, to thereby yield 2.66 g of a crude product. The crude product was suspended in methanol (20 mL), and a 2-mol/L aqueous sodium hydroxide solution (20 mL) was added thereto, followed by stirring for one hour at 60° C. After the temperature of the reaction mixture had been reduced to room temperature, water was added thereto, and the mixture was acidified with concentrated hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate anhydrate. The solvent was removed under reduced pressure, and the residue was recrystallized from chloroform-hexane, to thereby yield 1.88 g of the title compound as a yellow powder (81.7%).

Workup

  1. customwas reduced to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate anhydrate
  5. customthe solvent was removed through distillation
  6. additiona 2-mol/L aqueous sodium hydroxide solution (20 mL) was added
  7. stirringby stirring for one hour at 60° C
  8. customhad been reduced to room temperature
  9. additionwater was added
  10. extractionfollowed by extraction with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over sodium sulfate anhydrate
  13. customThe solvent was removed under reduced pressure
  14. customthe residue was recrystallized from chloroform-hexane

Sources & evidence

ORD record
ord-02499acd67234b30a0f1c5ad4eed1448
Source dataset
uspto-grants-2008_01
Patent number
US07314877B2

Reaction notes

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