Sodium Dithionite → 2-Chloro-6,7-difluoroquinoline-3-carboxylic acid

HRID 344874Notes

Reaction equation

HRID 344874 reaction equation
[Mn]([O-])(=O)(=O)=O.[K+].[Cl:7][C:8]1[NH:9][C:10]2[C:15]([CH2:16][C:17]=1[CH:18]=[O:19])=[CH:14][C:13]([F:20])=[C:12]([F:21])[CH:11]=2.S(S([O-])=O)([O-])=[O:23].[Na+].[Na+]>O.[OH-].[K+]>[Cl:7][C:8]1[C:17]([C:18]([OH:23])=[O:19])=[CH:16][C:15]2[C:10](=[CH:11][C:12]([F:21])=[C:13]([F:20])[CH:14]=2)[N:9]=1

Participants

6

Reactant 3

HCID 24489Sodium DithioniteHCID 516875Potassium PermanganateHCID 148533352-Chloro-6,7-difluoro-3-formyl-1,4-dihydroquinoline

Product 1

HCID 148533362-Chloro-6,7-difluoroquinoline-3-carboxylic acidYield 91.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14797Potassium HydroxideSolvent

Procedure

A solution of potassium permanganate (115 g) in water (1.215 liters) is added in the course of 1 hour to a stirred suspension, cooled to 10° C., of 2-chloro-6,7-difluoro-3-formyl-1,4-dihydro quinoline (70.18 g) in N aqueous potassium hydroxide solution (970 cc) while the temperature is maintained at between 10° and 14° C. The temperature is allowed to rise to approximately 20° C. and the mixture is stirred for a further 30 minutes at this temperature. Sodium dithionite (38.5 g) is added and the mixture is stirred for 10 minutes at a temperature in the region of 20° C., filtered through diatomaceous silica and washed with water (3×200 cc). The filtrate and the aqueous washing phases are combined and treated with 35% strength aqueous hydrochloric acid solution (140 cc). The precipitate formed is extracted with ethyl acetate (4×800 cc). The combined organic extracts are washed with water (2×500 cc), dried over magnesium sulphate, filtered and concentrated under reduced pressure (20 kPa) at 50° C. The residue is taken up with ethyl ether (400 cc), drained and washed with the same solvent (2×200 cc). 2-Chloro-6,7-difluoro-3-quinolinecarboxylic acid (49.2 g) is obtained in the form of a beige solid, m.p. 232° C., which is used without further purification for the subsequent steps.

Workup

  1. temperatureis maintained at between 10° and 14° C
  2. customto rise to approximately 20° C.
  3. stirringthe mixture is stirred for 10 minutes at a temperature in the region of 20° C.
  4. filtrationfiltered through diatomaceous silica
  5. washwashed with water (3×200 cc)
  6. additiontreated with 35% strength aqueous hydrochloric acid solution (140 cc)
  7. customThe precipitate formed
  8. extractionis extracted with ethyl acetate (4×800 cc)
  9. washThe combined organic extracts are washed with water (2×500 cc)
  10. dry with materialdried over magnesium sulphate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure (20 kPa) at 50° C
  13. washwashed with the same solvent (2×200 cc)

Sources & evidence

ORD record
ord-101f568a6f93468f8733b962779d37ef
Source dataset
uspto-grants-1991_10
Patent number
US05053509

Reaction notes

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