Methyl iodide → 3-bromo-4-chloro-N-(2-methoxy-phenyl)-N-methyl-benzamide

HRID 1848569Notes

Reaction equation

HRID 1848569 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[Cl:19])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][CH3:15])=[O:6].[H-].[Na+].I[CH3:23]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[Cl:19])[C:5]([N:7]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][CH3:15])[CH3:23])=[O:6]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 686027883-bromo-4-chloro-N-(2-methoxy-phenyl)-benzamide

Product 1

HCID 686027713-bromo-4-chloro-N-(2-methoxy-phenyl)-N-methyl-benzamideYield 78.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 3-bromo-4-chloro-N-(2-methoxy-phenyl)-benzamide (13.5 g, 39 mmol) in DMF (100 mL) at 0-5° C., was added NaH (1.9 g, 46.8 mmol, 60% in mineral oil) in several portions, followed by addition of iodomethane (3.15 mL, 50.7 mmol). The mixture was stirred at room temperature for 4 hrs and was partitioned between ethyl acetate and water. The organic layer was then washed with 1N HCl, saturated NaHCO3, brine and dried over MgSO4. Filtration over a silica gel pad followed by concentration and crystallization from ether/hexane yielded 3-bromo-4-chloro-N-(2-methoxy-phenyl)-N-methyl-benzamide (10.9 g) as a white solid. MS (M+H)+: 353.9, tR=2.812 min (method 1); NMR (CDCl3), δ, 7.62 (1H, d, J=1.5 Hz), 7.23-7.09 (3H, m), 7.06-7.00 (1H, m), 6.88-6.78 (2H, m), 3.75 (3H, s), 3.34 (3H, s)

Workup

  1. customwas partitioned between ethyl acetate and water
  2. washThe organic layer was then washed with 1N HCl, saturated NaHCO3, brine
  3. dry with materialdried over MgSO4
  4. filtrationFiltration over a silica gel pad
  5. concentrationfollowed by concentration and crystallization from ether/hexane

Sources & evidence

ORD record
ord-4dce87d57a2c4064bd41e95ecf9c954e
Source dataset
uspto-grants-2015_02
Patent number
US08952161B2

Reaction notes

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