Water → Ethyl 5-bromo-5'-methyl-2,3'-bipyridine-4-carboxylate

HRID 2047588Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:10]([Br:13])=[CH:11][N:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[N:19][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[Br:13][C:10]1[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3][C:2]([C:17]2[CH:18]=[N:19][CH:20]=[C:15]([CH3:14])[CH:16]=2)=[N:12][CH:11]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution ethyl 2,5-dibromoisonicotinate (1-2, 1.5 g, 4.86 mmol) in degassed dimethylformamide (24 mL) at 25° C. was added (5-methylpyridin-3-yl)boronic acid (0.665 g, 4.86 mmol), PdCl2dppf (0.355 g, 0.486 mmol), cesium carbonate (4.75 g, 14.6 mmol) and water (0.262 mL, 14.57 mmol). The reaction flask was purged with nitrogen, sealed and stirred at 50° C. overnight. 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 purified by normal phase column chromatography (0 to 50% EtOAc in hexanes) to afford the product (1-3) as a white solid. ESI+MS[M]+C14H13BrN2O2=321.0.

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
customthe crude product was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-5ebfb4a674c04f07ae2a65ce5bfc633e
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592457B2

Reaction notes

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