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

HRID 393326Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 393326
[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

Komponenten

6

Edukt 4

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

Produkt 1

HCID 100163706-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acidAusbeute 41,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-d591d28eeda547c891353a81667d6d53
Quelldatensatz
uspto-grants-2004_10
Patentnummer
US06806288B1

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