Hydrochloric Acid → 3-Hydroxy-6-methoxyquinoline-4-carboxylic acid

HRID 633808Notes

Reaction equation

HRID 633808 reaction equation
ClC[C:3](=O)[C:4]([OH:6])=[O:5].[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=O)[C:13]2=[O:20].[OH-].[K+].S([O-])(O)=O.[Na+].Cl>O.CO.C(#N)C.C(OCC)(=O)C>[OH:20][C:13]1[CH:14]=[N:15][C:16]2[C:12]([C:3]=1[C:4]([OH:6])=[O:5])=[CH:11][C:10]([O:9][CH3:8])=[CH:18][CH:17]=2

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 383335-MethoxyisatinHCID 151137Chloropyruvic acidHCID 23665763Sodium Bisulfite

Product 1

HCID 657101823-Hydroxy-6-methoxyquinoline-4-carboxylic acidYield 21.5%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Chloro-2-oxo-propionic acid (11.46 g, 91.10 mmol, 1.61 eq) is added portionwise at room temperature to a stirred solution of 5-methoxy-1H-indole-2,3-dione (10.0 g, 56.45 mmol, 1.0 eq) and potassium hydroxide (30.5 g, 543.6 mmol, 9.6 eq) in water (60 mL). After 6 days stirring at room temperature, a solution of sodium hydrogen sulfite (2.3 g, 22.10 mmol, 0.4 eq) in water (4 mL) is added and the reaction mixture is acidified by the addition of concentrated hydrochloric acid (12N, 30 mL). The resulting yellow precipitate is collected by filtration, washed successively with a saturated sulfur dioxide aqueous solution and water, then purified by column chromatography (silica gel, eluent: ethyl acetate:acetonitrile:methanol, 70:5:5, v/v/v) to afford 3-hydroxy-6-methoxyquinoline-4-carboxylic acid as a light brown solid (2.66 g, 21% yield).

Workup

  1. filtrationThe resulting yellow precipitate is collected by filtration
  2. washwashed successively with a saturated sulfur dioxide aqueous solution and water
  3. custompurified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-3de60a8a52684cc7b136d0f2346f7ddd
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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