Glycerol → 8-Methylquinoline-7-carboxylic acid

HRID 2365434Notes

Reaction equation

HRID 2365434 reaction equation
S(=O)(=O)(O)O.[NH2:6][C:7]1[C:8]([CH3:16])=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([OH:12])=[O:11].[I-].[Na+].[OH-].[Na+].[CH2:21](O)[CH:22](O)[CH2:23]O>O.CS(C)=O.CO>[CH3:16][C:8]1[C:9]([C:10]([OH:12])=[O:11])=[CH:13][CH:14]=[C:15]2[C:7]=1[N:6]=[CH:23][CH:22]=[CH:21]2

Participants

9

Reactant 5

HCID 753Glycerol2×HCID 1118Sulfuric AcidHCID 5238Sodium IodideHCID 14798Sodium HydroxideHCID 27336993-Amino-2-methylbenzoic acid

Product 1

HCID 597495658-Methylquinoline-7-carboxylic acid

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of concentrated sulfuric acid (21.74 ml) in water (16 ml), was added 3-amino-2-methylbenzoic acid (5 g; supplier Acros), 1,2,3-propanetriol (2.437 ml) and sodium iodide (0.104 g). The reaction mixture was heated to reflux for 2 hours at 150° C. Further 1,2,3-propanetriol (2.437 ml) was added and reaction mixture was refluxed for another two hours. The pH of the reaction mixture was adjusted to pH 3 by adding sodium hydroxide (12.5 M, 32.6 ml) then the mixture was filtered and the solid discarded. The aqueous phase was extracted with ethyl acetate and then the organic solvent was removed under vacuum to give crude product. This was dissolved in 1:1 DMSO & MeOH and purified by reverse phase chromatography and relevant fractions were combined and concentrated to afford the title compound (750 mg) as a white solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. customreaction mixture
  3. temperaturewas refluxed for another two hours
  4. filtrationthe mixture was filtered
  5. extractionThe aqueous phase was extracted with ethyl acetate
  6. customthe organic solvent was removed under vacuum
  7. customto give crude product
  8. custompurified by reverse phase chromatography and relevant fractions
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c7b119f9e2254a9e90025246cd571256
Source dataset
uspto-grants-2014_04
Patent number
US08697703B2

Reaction notes

Loading…