Cesium carbonate → Methyl 6-(2-fluorophenyl)-5'-methyl-3,3'-bipyridine-5-carboxylate
Reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=2)=[CH:4][C:3]=1[C:15]([O:17][CH3:18])=[O:16].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=2)=[CH:4][C:3]=1[C:15]([O:17][CH3:18])=[O:16]Participants
Conditions
- Temperature
- 40 °C
Procedure
To a solution of methyl 6-chloro-5′-methyl-3,3′-bipyridine-5-carboxylate (3-2, 4.25 g, 16.16 mmol) in degassed dimethylformamide (81 mL) at 25° C. was added 2-fluorophenylboronic acid (2.94 g, 21.01 mmol), PdCl2dppf (1.18 g, 1.62 mmol) and 4M aqueous cesium carbonate (10.1 mL, 40.4 mmol). The reaction flask was purged with nitrogen, sealed and stirred for 4 hours at 40° C. The crude reaction mixture was partitioned between water and EtOAc, separating layers and washing the organic layer with saturated sodium bicarbonate solution and brine. The solvent was removed by rotary evaporation and the crude product was taken up in DCM (40 mL). Quadrapure TU (6 g) was added and the mixture was stirred overnight at room temperature. Filtration and concentration afforded the title compound (3-3) as a solid. ESI+MS [M+H]+ C19H15FN2O2=323.1.
Workup
- customThe reaction flask was purged with nitrogen
- customsealed
- customThe crude reaction mixture
- customwas partitioned between water and EtOAc
- customseparating layers
- washwashing the organic layer with saturated sodium bicarbonate solution and brine
- customThe solvent was removed by rotary evaporation
- additionQuadrapure TU (6 g) was added
- stirringthe mixture was stirred overnight at room temperature
- filtrationFiltration and concentration
Sources & evidence
- ORD record
- ord-58b7f597227248f48f1946892d752c39
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08003797B2
Reaction notes
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