Malonic Acid → 2-Hydroxyquinoline

HRID 2352999Notes

Reaction equation

HRID 2352999 reaction equation
Br[C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][C:3]=1OC.[C:11](O)(=O)[CH2:12][C:13](O)=[O:14].P(Cl)(Cl)(Cl)=O>>[NH:8]1[C:7]2[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:11]=[CH:12][C:13]1=[O:14]

Participants

4

Reactant 3

HCID 867Malonic AcidHCID 24813Phosphorus oxychlorideHCID 109105752-Bromo-3-methoxyaniline

Product 1

HCID 60382-Hydroxyquinoline

Conditions

Temperature
95 °C

Procedure

To 2-bromo-3-aminoanisole 2B4 (378 mg, 1.87 mmol, 1 eq) and malonic acid (194 mg, 1.87 mmol) was added phosphorous oxychloride (175 μL, 1.87 mmol). The reaction was placed in a pre-heated bath (95° C.) and stirred for 30 minutes. The mixture was cooled, and diluted with ice water and stirred ca. 2 h to afford a grey solid. This was filtered and washed with water until free of acid and then taken up into 1N NaOH. Insoluble material was removed by filtration and the resulting aqueous solution was treated with EtOH (8 mL) before adjusting the pH to 5-6 with 1N HCl (aq). The desired product was filtered and dried to afford quinolone 3J1 (0.12 g, 24%) as a yellow solid. MS: 270.0 (M+H)+ and 291.9 (M+Na)+.

Workup

  1. customThe reaction was placed in a pre-heated bath
  2. temperatureThe mixture was cooled
  3. stirringstirred ca. 2 h
  4. customto afford a grey solid
  5. filtrationThis was filtered
  6. washwashed with water until free of acid
  7. customInsoluble material was removed by filtration
  8. additionthe resulting aqueous solution was treated with EtOH (8 mL)
  9. filtrationThe desired product was filtered
  10. customdried

Sources & evidence

ORD record
ord-6e5104ad18154ae8b7d4276cca947f21
Source dataset
uspto-grants-2010_07
Patent number
US07749961B2

Reaction notes

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