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

HRID 335389Notes

Reaction equation

HRID 335389 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][CH:13]=[C:14]([C:20]([O:22]CC)=O)[C:15]([O:17]CC)=[O:16].CC(O)C.O.[OH-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:9])([F:10])[F:11])=[C:4]2[C:3]=1[NH:12][CH:13]=[C:14]([C:15]([OH:17])=[O:16])[C:20]2=[O:22]

Participants

6

Reactant 4

HCID 962Water2×HCID 3776IsopropanolHCID 14798Sodium Hydroxide2×HCID 2797069Diethyl 2-((2-chloro-5-(trifluoromethyl)phenylamino)methylene)malonate

Product 1

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

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

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

Workup

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

Sources & evidence

ORD record
ord-fcf779ba90fd407b9a38fd4b57773fbc
Source dataset
uspto-grants-2014_11
Patent number
US08884018B2

Reaction notes

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