Ethanol → Methyl 4-chloro-6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]-oxy}phenyl)methyl]-2-Pyridinecarboxylate

HRID 2356623

Reaktionsgleichung

Reaktionsgleichung von HRID 2356623
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8]Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1.C(O)C.[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[F:36])=[C:22](B(O)O)[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][C:20]2[CH:19]=[C:18]([Cl:17])[CH:23]=[CH:22][C:21]=2[O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[F:36])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1

Komponenten

7

Edukt 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 59384250(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)boronic acidHCID 68456565Methyl 4-chloro-6-(chloromethyl)pyridine-2-carboxylate

Produkt 1

HCID 68458580Methyl 4-chloro-6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]-oxy}phenyl)methyl]-2-PyridinecarboxylateAusbeute 12,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

To a stirring solution of methyl 4-chloro-6-(chloromethyl)-2-pyridinecarboxylate (175 mg), in dry toluene (4 ml) and ethanol (4 ml) was added (5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)boronic acid (250 mg), potassium carbonate (330 mg) and tetrakis(triphenylphosphine)-palladium(0) (92 mg). The mixture was stirred under reflux for 2 hours. Solvent was removed u.r.p. (under reduced pressure) and water (20 ml) and ether (20 ml) added to the residue. Insoluble solid was filtered off over Hyflo and washed with ether. The aqueous layer was separated off and washed with ether (15 ml), and the combined ether layers washed with brine (10 ml), dried over MgSO4 and evaporated down u.r.p. The residue was purified by mass-directed autopreparation to give a white solid (46.3 mg, 12.8%). LC/MS [MH+]=468/470/472, Rt=4.11 min. NMR and LC/MS indicated that trans-esterification had occurred to give the ethyl ester.

Aufarbeitung

  1. temperatureunder reflux for 2 hours
  2. customSolvent was removed u.r.p
  3. addition(under reduced pressure) and water (20 ml) and ether (20 ml) added to the residue
  4. filtrationInsoluble solid was filtered off over Hyflo
  5. washwashed with ether
  6. customThe aqueous layer was separated off
  7. washwashed with ether (15 ml)
  8. washthe combined ether layers washed with brine (10 ml)
  9. dry with materialdried over MgSO4
  10. customevaporated down u.r.p
  11. customThe residue was purified by mass-directed autopreparation

Quellen und Nachweise

ORD-Eintrag
ord-206a81332f8d48e19ef464c15d786400
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07759369B2

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