Potassium Carbonate → Methyl 6-(5-fluoro-2-hydroxyphenyl)nicotinate

HRID 602117Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 602117
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6](B(O)O)[CH:7]=1.Cl[C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=2)[CH:7]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 37724765-Fluoro-2-hydroxyphenylboronic acid

Produkt 1

HCID 136359921Methyl 6-(5-fluoro-2-hydroxyphenyl)nicotinateAusbeute 57,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysator2×HCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a degassed mixture of 1,4-dioxane:water (4:1, 15 mls) was added (5-fluoro-2-hydroxyphenyl)boronic acid (0.781 g, 5.0 mmol), methyl 6-chloronicotinate (0.86 g, 5.0 mmol), potassium carbonate (2.08 g, 15.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.29 g, 0.05 mmol) and the resulting mixture stirred at 80° C. for 2 h. After this time additional tetrakis(triphenylphosphine)palladium(0) (0.29 g, 0.05 mmol) was added and then heating continued at 80° C. for 3 h. The mixture was then stirred at room temperature overnight. The solvent was evaporated in vacuo and the residue suspended in ethyl acetate (50 ml). The suspension was filtered through a plug of arbocel and the filtrate concentrated in vacuo. The resulting residue was dissolved in ethyl acetate (100 ml) and washed with saturated aqueous sodium carbonate (3×100 ml). The aqueous washings were combined and extracted with ethyl acetate (3×50 ml). The ethyl acetate layers were combined, dried with anhydrous MgSO4 and concentrated in vacuo to afford a solid which was recrystallised from dichloromethane/heptane to afford the title compound as a yellow solid (0.71 g) (57%). 1H NMR (400 MHz, CDCl3) □ ppm 9.14 (1H, s), 8.46-8.40 (1H, m), 7.91-7.86 (1H, m) 7.53-7.46 (1H, m), 7.11-7.03 (1H, m), 7.02-6.96 (1H, m), 3.99 (3H, s). LRMS: AP m/z 248 [M+H]+.

Aufarbeitung

  1. temperatureheating
  2. waitcontinued at 80° C. for 3 h
  3. stirringThe mixture was then stirred at room temperature overnight
  4. customThe solvent was evaporated in vacuo
  5. filtrationThe suspension was filtered through a plug of arbocel
  6. concentrationthe filtrate concentrated in vacuo
  7. dissolutionThe resulting residue was dissolved in ethyl acetate (100 ml)
  8. washwashed with saturated aqueous sodium carbonate (3×100 ml)
  9. extractionextracted with ethyl acetate (3×50 ml)
  10. dry with materialdried with anhydrous MgSO4
  11. concentrationconcentrated in vacuo
  12. customto afford a solid which
  13. customwas recrystallised from dichloromethane/heptane

Quellen und Nachweise

ORD-Eintrag
ord-8a4d714d378c44c9a55fbecc10f20854
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902373B2

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