Acetic Acid → 8-Chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid

HRID 1952189Notes

Reaction equation

HRID 1952189 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:18]([F:21])([F:20])[F:19])=[C:6]2[C:11]=1[NH:10][CH:9]=[C:8]([C:12]([O:14]CC)=[O:13])[C:7]2=[O:17].CC(O)C.[OH-].[Na+].C(O)(=O)C>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:18]([F:21])([F:19])[F:20])=[C:6]2[C:11]=1[NH:10][CH:9]=[C:8]([C:12]([OH:14])=[O:13])[C:7]2=[O:17]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 3776IsopropanolHCID 14798Sodium HydroxideHCID 13337379Ethyl 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 42541548-Chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acidYield 88.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Ethyl 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate (15) (1200 g, 3.754 mol) was charged into a reaction vessel followed by the addition of 2-propanol (1.200 L) and water (7.200 L) and stirred. Sodium hydroxide (600.6 g, 7.508 mol) and water (1.200 L) were mixed and allowed to cool to room temperature. The resulting mixture was charged into the reaction vessel and then was heated to 80° C. and stirred for 3.5 h to generate a dark, homogenous mixture. After an additional hour, acetic acid (9.599 L of 20% w/v, 31.97 mol) was added via dropping funnel over 45 min. The reaction mixture was cooled with stirring to 22° C. at a rate of 6° C./h. The resulting solid was filtered and washed with water (3 L) to generate a wet cake (1436 g). The filtrate was dried in a vacuum oven with a nitrogen bleed over Drierite® to generate 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid as a brown solid (1069 g). The 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid was purified by slurrying in 1.5 L methanol and stirring for 6 h. It was then filtered and dried to furnish 968.8 g of purified 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid.

Workup

  1. additionThe resulting mixture was charged into the reaction vessel
  2. temperaturewas heated to 80° C.
  3. stirringstirred for 3.5 h
  4. waitAfter an additional hour
  5. customover 45 min
  6. temperatureThe reaction mixture was cooled
  7. stirringwith stirring to 22° C. at a rate of 6° C./h
  8. filtrationThe resulting solid was filtered
  9. washwashed with water (3 L)
  10. customThe filtrate was dried in a vacuum oven with a nitrogen
  11. customThe 8-chloro-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid was purified
  12. stirringstirring for 6 h
  13. filtrationIt was then filtered
  14. customdried

Sources & evidence

ORD record
ord-41b6d26377e5449da1bbea4e7ffc5577
Source dataset
uspto-grants-2013_03
Patent number
US08404849B2

Reaction notes

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