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

HRID 1485924Notes

Reaction equation

HRID 1485924 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-d7bcbb3bff084d0692f2cb0eb56f2221
Source dataset
uspto-grants-2016_08
Patent number
US09422310B2

Reaction notes

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