Cesium carbonate → 5-Fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid ethyl ester
Reaktionsgleichung
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[N:7][C:6]=1Cl)[CH3:2].[CH3:14][S:15][C:16]1[CH:17]=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[N:7][C:6]=1[O:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([S:15][CH3:14])[CH:17]=1)[CH3:2]Komponenten
Edukt 3
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- 100 °C
Versuchsvorschrift
A solution of ethyl-2-chloro-5-fluoro-nicotinoate (J. Med. Chem., 1993, 36(18), 2676–88) (29 g, 0.143 mol) and 3-methylsulphanyl-phenol (WO 98/45268, pg. 68, preparation 61) (20 g, 0.143 mol) in dioxane (300 mL) was treated with caesium carbonate (46.5 g, 0.143 mol) at room temperature. The reaction mixture was heated to 100° C. and stirred for 48 hours. The reaction mixture was concentrated in vacuo and the residue taken up in water (600 mL) and extracted with ethyl acetate (3×250 mL). The organics were combined, washed with brine (200 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5) to yield the title product as a yellow oil, 27.1 g.
Aufarbeitung
- concentrationThe reaction mixture was concentrated in vacuo
- extractionextracted with ethyl acetate (3×250 mL)
- washwashed with brine (200 mL)
- dry with materialdried over magnesium sulphate
- concentrationconcentrated in vacuo
- customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5)
Quellen und Nachweise
- ORD-Eintrag
- ord-438200328f744bb98da3039fbbb214c1
- Quelldatensatz
- uspto-grants-2006_11
- Patentnummer
- US07141586B2
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