Sodium Hydroxide → 1,2-Dihydro-6-(trifluoromethoxy)-2-(trifluoromethyl)-3-quinolinecarboxylic acid

HRID 2297887Notes

Reaction equation

HRID 2297887 reaction equation
[F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]([C:14]([F:17])([F:16])[F:15])[C:8]([C:18]([O:20]CC)=[O:19])=[CH:7]2.[OH-].[Na+]>CO.O>[F:24][C:2]([F:1])([F:23])[O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]([C:14]([F:15])([F:16])[F:17])[C:8]([C:18]([OH:20])=[O:19])=[CH:7]2

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 21883532Ethyl 1,2-dihydro-6-(trifluoromethoxy)-2-(trifluoromethyl)-3-quinolinecarboxylate

Product 1

HCID 218836841,2-Dihydro-6-(trifluoromethoxy)-2-(trifluoromethyl)-3-quinolinecarboxylic acidYield 89%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

The ethyl 1,2-dihydro-6-(trifluoromethoxy)-2(trifluoromethyl)-3-quinolinecarboxylate from Step 4 (880 mg, 2.5 mmol) and 2.5 N aqueous sodium hydroxide (2 mL) were mixed in methanol (15 mL) and water (15 mL). The solution was heated on a steam bath for 2 hours. The reaction was allowed to cool to room temperature and was extracted with diethyl ether (50 mL). The aqueous layer was acidified (pH=1) with 3 N HCl and extracted with ethyl acetate (2×50 mL). The combined ethyl acetate extracts were dried over MgSO4 and concentrated in vacuo leaving an oil. The oil was crystallized from cold dichloromethane-hexanes to afford the 1,2-dihydro-6-(trifluoromethoxy)-2(trifluoromethyl)-3-quinolinecarboxylic acid as yellow needles (0.727 g, 89%): mp 127.7-128.9° C. 1H NMR (CDCl3, 300 MHz) 7.80 (s, 1H), 7.05 (m, 2H), 6.62 (d, 1H, J=8.0 Hz), 5.13 (m, 1H), 4.62 (brs, 1H). ESHRMS m/z 326.0252 (M−H, Calc'd 326.0252). Anal. Calc'd for C12H7NO3F6: C, 44.05; H, 2.16; N, 4.28. Found: C, 43.89; H, 2.04; N, 4.24.

Workup

  1. temperatureThe solution was heated on a steam bath for 2 hours
  2. extractionwas extracted with diethyl ether (50 mL)
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined ethyl acetate extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customleaving an oil
  7. customThe oil was crystallized from cold dichloromethane-hexanes

Sources & evidence

ORD record
ord-32f8e684c8754dfbafe0c9e3ae5dc40e
Source dataset
uspto-grants-2002_12
Patent number
US06492390B2

Reaction notes

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