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

HRID 1422886Notes

Reaction equation

HRID 1422886 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>[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

7

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 1

HCID 962WaterSolvent2×

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 with a saturated sulfur dioxide aqueous solution and water, then purified by column chromatography (silica gel, eluent:ethyl acetate:acetonitrile:methanol:water, 70:5:2.5:2.5, v/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 with a saturated sulfur dioxide aqueous solution and water
  3. custompurified by column chromatography (silica gel, eluent:ethyl acetate:acetonitrile:methanol:water, 70:5:2.5:2.5, v/v/v/v)

Sources & evidence

ORD record
ord-e836f5b5e2924bc581c96d7ece0f519b
Source dataset
uspto-grants-2015_01
Patent number
US08927541B2

Reaction notes

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