Methanol → 6-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid

HRID 2297884Notes

Reaction equation

HRID 2297884 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18]CC)=[O:17])=[CH:5]2.[OH-].[Na+].CO.O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:13])[F:14])[C:6]([C:16]([OH:18])=[O:17])=[CH:5]2

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 21883646Ethyl 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

Product 1

HCID 100163706-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acidYield 41.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The ester from Step 2 (1.7 g, 5.6 mmol) and 2.5 N sodium hydroxide (4.4 mL, 11 mmol) were mixed in tetrahydrofuran (25 mL), methanol (10 mL), and water (25 mL). After stirring overnight, contents were concentrated in vacuo to remove the THF and methanol. The aqueous solution remaining was extracted with diethyl ether (2×100 mL). The resulting aqueous layer was acidified with 2 N HCl causing the precipitation of an oil. The oil was purified by flash chromatography on silica gel, eluting with ethyl acetate-hexanes (1:1). Fractions containing the desired product were combined, and concentrated in vacuo. The residue was triturated with dichloromethane, and filtered to afford the 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid as a yellow solid (0.645 g, 41%): mp 187.8-188.8° C. 1H NMR (acetone-d6, 300 MHz) 7.69 (s, 1H), 7.36 (s, 1H), 7.15 (d, 1H, J=8.0 Hz), 6.83 (d, 1H, J=8.0 Hz), 6.60 (brs, 1H), 5.20 (m, 1H). ESHRMS m/z 276.0040 (M−H, Calc'd 276.0039). Anal. Calc'd for C11H7NO2F3Cl+2.6% H2O: C, 46.39; H, 2.98; N, 4.92. Found: C, 45.99; H, 2.54; N, 4.85.

Workup

  1. concentrationcontents were concentrated in vacuo
  2. customto remove the THF and methanol
  3. extractionThe aqueous solution remaining was extracted with diethyl ether (2×100 mL)
  4. customthe precipitation of an oil
  5. customThe oil was purified by flash chromatography on silica gel
  6. washeluting with ethyl acetate-hexanes (1:1)
  7. additionFractions containing the desired product
  8. concentrationconcentrated in vacuo
  9. customThe residue was triturated with dichloromethane
  10. filtrationfiltered

Sources & evidence

ORD record
ord-237f02aa276a4a0ab6188f118e50817c
Source dataset
uspto-grants-2002_12
Patent number
US06492390B2

Reaction notes

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