Citric Acid → HCID 21249290, compound

HRID 1194707Notes

Reaction equation

HRID 1194707 reaction equation
[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH2:3][CH2:2]1.[C:12](OCC)(=[O:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14].[H-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1>[C:12]([CH:3]1[C:4](=[O:11])[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[O:1][CH2:2]1)([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:18]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 68110Chromanone

Product 1

HCID 21249290HCID 21249290, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of 4-chromanone (11.2 g) and diethyl oxalate (13.3 g) in anhydrous dioxane (75 ml) is added under stirring at room temperature to a suspension of 50% sodium hydride (4 g) in anhydrous dioxane (150 ml). The mixture is allowed to react under stirring at 80° C. for 3.5 hours. After cooling, the reaction mixture is diluted with ice water and acidified to pH 4 with 40% citric acid aqueous solution. The oily precipitate is extracted with ethyl acetate, then the organic solution is washed with 40% citric acid and water until neutral. After evaporation of the solvent in vacuo the residue is purified over a SiO2 column using hexane/ethyl acetate 80:20 as eluent. Crystallization from isopropyl alcohol gives 3-ethoxalylchroman-4-one, m.p. 73°-75° C. (7.7 g), which is reacted with phenylhydrazine (3.68 g) in acetic acid (80 ml) at a temperature varying between 25° C. and about 40° C. for 30 minutes. The reaction mixture is diluted with ice water and then neutralized with 30% ammonium hydroxide. The precipitate is filtered and washed with water. Crystallization from isopropyl alcohol gives 1,4-dihydro-1-phenyl-[1]-benzopyrano[4,3-c]pyrazole-3-carboxylic acid, ethyl ester, m.p. 154°-156° C. (7.4 g), which is reacted with acetonitrile (74 ml) in dioxane (45 ml) in the presence of 50% sodium hydride (2.2 g) under stirring at 60° C. for 30 minutes. After cooling the reaction mixture is diluted with ice water and acidified to pH 4 with citric acid. The precipitate is filtered and washed with water and purified over a SiO2 column, using chloroform as eluent.

Workup

  1. customto react
  2. temperatureAfter cooling
  3. extractionThe oily precipitate is extracted with ethyl acetate
  4. washthe organic solution is washed with 40% citric acid and water until neutral
  5. customAfter evaporation of the solvent in vacuo the residue
  6. customis purified over a SiO2 column
  7. customCrystallization from isopropyl alcohol

Sources & evidence

ORD record
ord-7a79a4dd9d73461aa6c8019fb70c15fa
Source dataset
uspto-grants-1989_03
Patent number
US04816467

Reaction notes

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