Dimethylformamide → HCID 67065843, compound

HRID 1748711Notes

Reaction equation

HRID 1748711 reaction equation
C[C:2]1[C:3]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.BrBr.[C:16]([NH:19][CH:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:21]([O:23][CH2:24][CH3:25])=[O:22])(=[O:18])[CH3:17].[H-].[Na+].[CH3:33]N(C=O)C>CCOC(C)=O.C1C=CC=CC=1.O>[N:9]1[CH:10]=[C:11]([CH2:33][C:20]([NH:19][C:16](=[O:18])[CH3:17])([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:12]=[CH:13][C:8]=1[C:3]1[CH:2]=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

9

Reactant 5

HCID 6228Dimethylformamide2×HCID 14041Acetamidomalonic acid diethyl esterHCID 24408BromineHCID 24758Sodium hydrideHCID 1824573-Methyl-2,2'-bipyridine

Product 1

HCID 67065843HCID 67065843, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Methyl-2,2′-bipyridine (1.7 g, 10 mmol) in a mixed solvent (100 mL) of water and benzene (1:1) was irradiated and refluxed using a halogen lamp (150 W). Bromine (1.6 g, 10 mmol) was added and the mixture was heated to reflux for 30 min. The solution was concentrated under reduced ressure and dissolved in EtOAc. The organic layer was washed with saturated aqueous NaHCO3 solution, dried over MgSO4, and concentrated under reduced pressure to afford the crude brominated product. A mixture of diethyl acetamidomalonate (2.6 g, 12 mmol) and sodium hydride (0.48 g, 12 mmol, 60% in mineral oil) in dry DMF (50 mL) was stirred for 30 min at 0° C. To the solution was added the crude product in dry DMF (20 mL) at 0° C. and the mixture was stirred for 1 h at room temperature. The reaction mixture was diluted with EtOAc (200 mL) and washed with a 10% aqueous sodium thiosulfate solution (2×150 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (0.5% MeOH in CH2Cl2) to give diethyl 2-(2,2′-bipyridin-5-ylmethyl)-2-acetamidomalonate (2.5 g, 65%) as a white solid. 1H-NMR (500 MHz, CDCl3): 1.38 (m, 6H), 2.15 (s, 3H), 3.81 (s, 2H), 4.35 (m, 4H), 6.68 (s, 1H), 7.36 (dd, 1H), 7.55 (dd, 1H), 7.87 (m, 1H), 8.36 (d, 1H), 8.41 (d, 1H), 8.42 (d, 1H), 8.74 (dd, 1H).

Workup

  1. temperaturerefluxed
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 30 min
  4. concentrationThe solution was concentrated under reduced ressure
  5. dissolutiondissolved in EtOAc
  6. washThe organic layer was washed with saturated aqueous NaHCO3 solution
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customto afford the crude brominated product
  10. stirringthe mixture was stirred for 1 h at room temperature
  11. washwashed with a 10% aqueous sodium thiosulfate solution (2×150 mL)
  12. dry with materialThe organic layer was dried over MgSO4
  13. concentrationconcentrated under reduced pressure
  14. customThe crude product was purified by flash column chromatography (0.5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-f474b2ee9bbc47339e43c65346660f8e
Source dataset
uspto-grants-2015_10
Patent number
US09150849B2

Reaction notes

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