Azobisisobutyronitrile → Methyl 5-(bromomethyl)-6-methoxynicotinate

HRID 1432877Notes

Reaction equation

HRID 1432877 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([O:11][CH3:12])=[N:6][CH:5]=1.C1C(=O)N([Br:21])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([CH2:10][Br:21])[C:7]([O:11][CH3:12])=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 54292198Methyl 6-methoxy-5-methylpyridine-3-carboxylate

Product 1

HCID 53756612Methyl 5-(bromomethyl)-6-methoxynicotinateYield 54%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

A solution containing 6-methoxy-5-methyl-nicotinic acid methyl ester (4.00 g, 22.1 mmol), NBS (5.11 g, 28.7 mmol), and AIBN (0.90 g, 5.5 mmol) in CCl4 (100 mL) is warmed to reflux. After 5 h, the reaction mixture is cooled and then concentrated in vacuo. The residue is dissolved in EtOAc (500 mL) and washed successively with aqueous Na2S2O3 (300 mL), water (100 mL), brine then dried over anhydrous Na2SO4, filtered and concentrated. The crude product is purified by silica gel flash column chromatography (hexane/diethyl ether, 9:1) to provide 3.10 g (54%) of the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ3.90 (s, 3H), 4.07 (s, 3H), 4.46 (s, 2H), 8.19 (d, J=2.2 Hz, 1H), 8.79 (d, J=2.2 Hz, 1H) ppm; MS (EI): m/z 259 (M+).

Workup

  1. temperatureis warmed to reflux
  2. temperaturethe reaction mixture is cooled
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue is dissolved in EtOAc (500 mL)
  5. washwashed successively with aqueous Na2S2O3 (300 mL), water (100 mL), brine
  6. dry with materialthen dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by silica gel flash column chromatography (hexane/diethyl ether, 9:1)

Sources & evidence

ORD record
ord-690a6db5750a4dc49cf7b0dea202de42
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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