Methyl iodide → Methyl 6-(ethylsulfonyl)-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245260Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245260
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1)[C:6]([CH3:24])=[C:5]2[C:25]([O:27][CH3:28])=[O:26].[CH2:29]([S:31]([OH:33])=[O:32])[CH3:30].[Na].IC>CN1CCCC1=O.CS(C)=O.C(Cl)Cl.O.[Cu]I>[CH2:29]([S:31]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1)[C:6]([CH3:24])=[C:5]2[C:25]([O:27][CH3:28])=[O:26])(=[O:33])=[O:32])[CH3:30]

Komponenten

10

Edukt 4

HCID 6328Methyl iodide2×HCID 435496Ethanesulfinic acidHCID 5360545SodiumHCID 67384067Methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Produkt 1

HCID 67384351Methyl 6-(ethylsulfonyl)-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2 g, 4.40 mmol) in N-methyl-2-pyrrolidone (15 mL) and DMSO (30 mL) was added copper(I) iodide (2.52 g, 13.21 mmol) followed by ethanesulfinic acid, sodium salt (1.534 g, 13.21 mmol). The mixture was evacuated and purged with N2 three times and heated at 120° C. for 16 h. The mixture was cooled to room temperature, and iodomethane (1.377 mL, 22.01 mmol) was added. After 90 min, additional iodomethane (1.377 mL, 22.01 mmol) was added and the mixture was stirred for an additional hour. The mixture was diluted with methylene chloride and water, and the biphasic solution was filtered through Celite®. The phases were separated, and the aqueous phase was extracted with methylene chloride (50 mL). The combined organic extracts were washed with water (3×50 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was loaded onto florisil and purified via column chromatography (ISCO, 40 g silica, 5-55% ethyl acetate/hexanes) to give methyl 6-(ethylsulfonyl)-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.95 g, 76% yield). MS (m/z) 468.0 (M+H+).

Aufarbeitung

  1. customThe mixture was evacuated
  2. custompurged with N2 three times
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationthe biphasic solution was filtered through Celite®
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with methylene chloride (50 mL)
  7. washThe combined organic extracts were washed with water (3×50 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. custompurified via column chromatography (ISCO, 40 g silica, 5-55% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-ebc50067082e4361af932c9ebc81c048
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658636B2

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