Hydrochloric Acid → 6-Cyano-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid

HRID 2297893Notes

Reaction equation

HRID 2297893 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]([C:13]([F:16])([F:15])[F:14])[C:7]([C:17]([O:19]CC)=[O:18])=[CH:6]2)#[N:2].[OH-].[Li+].Cl.C(OCC)C>CO.O1CCCC1.O>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]([C:13]([F:15])([F:16])[F:14])[C:7]([C:17]([OH:19])=[O:18])=[CH:6]2)#[N:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 3939Lithium HydroxideHCID 21883651Ethyl 6-cyano-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

Product 1

HCID 218836646-Cyano-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a suspension of ethyl 6-cyano-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate (140 mg, 0.45 mmol) in methanol-tetrahydrofuran-water (10 mL, 7:2:1) was added lithium hydroxide (76 mg, 0.91 mmol) and the mixture gently heated to reflux for two hours. The contents were cooled to room temperature and 1 N aqueous hydrochloric acid added until pH=1. The organic solvent was removed in vacuo to afford a suspension of crude yellow solid. Diethyl ether (20 mL) was added, and the solution was washed with water (2×20 mL), saturated ammonium sulfate (2×20 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield 6-cyano-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid as a yellow solid, (116 mg, 95%): mp 238-240° C. 1H NMR (CD3OD/300 MHz) 7.75 (s, 1H), 7.56 (m, 1H), 7.43 (m, 1H), 6.79 (d, 1H, J=8.5 Hz) 5.19 (q, 1H, J=7.1 Hz). EIHRMS m/z 267.0405 (M−H, Calc'd 267.0381). Anal. Calc'd for C14H11F3N2O2: C, 53.74; H, 2.63; N, 10.45. Found: C, 53.99; H, 2.89; N, 10.19.

Workup

  1. temperaturethe mixture gently heated
  2. temperatureto reflux for two hours
  3. customThe organic solvent was removed in vacuo
  4. customto afford
  5. additiona suspension of crude yellow solid
  6. washthe solution was washed with water (2×20 mL), saturated ammonium sulfate (2×20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-b9904a64c89e455baa19ff8832fb57e8
Source dataset
uspto-grants-2002_12
Patent number
US06492390B2

Reaction notes

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