Hydrochloric Acid → 6-Chloro-1,2-dihydro-1-methyl-2-(trifluoromethyl)-3-quinoline-carboxylic acid

HRID 2297895Notes

Reaction equation

HRID 2297895 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19]CC)=[O:18])=[CH:5]2.[OH-].[Li+].Cl.C(OCC)C>CO.O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]([C:13]([F:16])([F:14])[F:15])[C:6]([C:17]([OH:19])=[O:18])=[CH:5]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 3939Lithium HydroxideHCID 21883533Ethyl 6-chloro-1,2-dihydro-1-methyl-2-(trifluoro-methyl)-3-quinolinecarboxylate

Product 1

HCID 98145666-Chloro-1,2-dihydro-1-methyl-2-(trifluoromethyl)-3-quinoline-carboxylic acidYield 98%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Ethyl 6-chloro-1,2-dihydro-1-methyl-2-(trifluoro-methyl)-3-quinolinecarboxylate(1.21 g, 3.78 mmol) was suspended in methanol-tetrahyrofuran-water (20 mL, 7:2:1). Lithium hydroxide (0.262 g, 6.24 mmol) was added, and the mixture was gently heated to reflux for two hours. The reaction was cooled to room temperature and 1 N HCl added until pH=1. The organic solvent was removed in vauco to afford a suspension of crude yellow solid. Diethyl ether (20 mL) was added, and the resulting solution was washed with water (2×20 mL), saturated ammonium chloride (2×20 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to afford the product as a yellow solid, 6-chloro-1,2-dihydro-1-methyl-2-(trifluoromethyl)-3-quinoline-carboxylic acid. (1.08 g, 98% yield): mp 208-209° C. 1H NMR (CD3OD/300 MHz) 7.69 (d, 1H, J=2.5 Hz), 7.28-7.24 (m, 2H), 6.73 (dd, 1H, J=9.5, 2.5 Hz), 5.13 (q, 1H, J=7.0), 3.16 (s, 3H). Anal. Calc'd for C12H9F3NO2Cl: C, 49.42; H, 3.11; N, 4.80; Cl, 12.16. Found: C, 49.88; H, 3.29; N, 4.59; Cl, 12.42

Workup

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

Sources & evidence

ORD record
ord-973af833cb534430a42c7a0ade61c01c
Source dataset
uspto-grants-2002_12
Patent number
US06492390B2

Reaction notes

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