Cesium carbonate → Methyl 3-[(4-fluorobenzyl)amino]pyridine-4-carboxylate
Reaktionsgleichung
Br[C:2]1[CH:11]=[N:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH2:18])=[CH:15][CH:14]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH:18][C:2]2[CH:11]=[N:10][CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:15][CH:14]=1Komponenten
Edukt 4
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 2
Reaktionsbedingungen
- Temperatur
- 116 °C
Versuchsvorschrift
Methyl 3-bromoisonicotinate (220 mg, 1.02 mmol), 4-fluorobenzylamine (132 μL, 1.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (47 mg, 0.051 mmol), Xantphos (89 mg, 0.153 mmol), and cesium carbonate (500 mg, 1.53 mmol) were combined in dioxane (4 mL) under N2 in a sealed microwave tube. The reaction mixture was heated at 116° C. in a microwave for 1 h. The mixture was then filtered, washing with DCM, to remove solids. The solution was concentrated in vacuo and purified by silica gel chromatography (20-50% EtOAc/hexanes) to give 228 mg (88%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.93 (d, 1H, J=5.0 Hz), 7.79 (br s, 1H), 7.63 (d, 1H, J=5.0 Hz), 7.27-7.34 (m, 2H), 7.03 (t, 2H, J=8.6 Hz), 4.47 (d, 2H, J=5.6 Hz), 3.89 (s, 3H). [M+H] calc'd for C14H13FN2O2, 261. found 261.
Aufarbeitung
- filtrationThe mixture was then filtered
- washwashing with DCM
- customto remove solids
- concentrationThe solution was concentrated in vacuo
- custompurified by silica gel chromatography (20-50% EtOAc/hexanes)
Quellen und Nachweise
- ORD-Eintrag
- ord-5299fbe2b67248b4acd98ddddd7bce30
- Quelldatensatz
- uspto-grants-2016_09
- Patentnummer
- US09447045B2
Notizen zur Reaktion
Wird geladen…