Triethylamine → 2-amino-5-bromo-N-methoxy-N-methylbenzamide

HRID 50688Notes

Reaction equation

HRID 50688 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(CC)CC)C.[Br:13][C:14]1[CH:25]=[C:18]2[C:19]([O:21]C(=O)[NH:23][C:17]2=[CH:16][CH:15]=1)=O>C(O)C.O>[NH2:23][C:17]1[CH:16]=[CH:15][C:14]([Br:13])=[CH:25][C:18]=1[C:19]([N:3]([O:4][CH3:5])[CH3:2])=[O:21]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2885615-Bromoisatoic Anhydride

Product 1

HCID 159081302-amino-5-bromo-N-methoxy-N-methylbenzamideYield 68%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×

Procedure

To a mixture of N,O-dimethylhydroxylamine hydrochloride (9.42 g, 96 mmol) and triethyl amine (13.5 mL, 96 mmol) in ethanol and water (100 mL/10 mL) was added a solution of 5-bromoisatoic anhydride (20 g, 74 mmol) in ethanol and water (100 mL/10 mL) at ambient temperature under nitrogen. The reaction mixture was heated at reflux for 3 hours. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL), washed with 1N aqueous sodium hydroxide solution (2×20 mL), brine (30 mL), and dried with MgSO4. After removal of the solvent, the residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/3:2) to give 2-amino-5-bromo-N-methoxy-N-methylbenzamide as an off-white solid (13 g, 68%): mp 80-81° C.; 1H-NMR (CDCl3) δ 7.49 (d, 1H, J=2.1 Hz), 7.26 (dd, 1H, J=8.3, 2.0 Hz), 6.59 (d, 1H, J=8.4 Hz), 4.69 (br, 2H), 3.58 (s, 3H), 3.34 (s, 3H); Anal. Calc. For C9H11BrN2O2: C, 41.72; H, 4.28; N, 10.81. Found: C, 41.99; H, 4.16; N, 10.82.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (100 mL)
  5. washwashed with 1N aqueous sodium hydroxide solution (2×20 mL), brine (30 mL)
  6. dry with materialdried with MgSO4
  7. customAfter removal of the solvent
  8. customthe residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/3:2)

Sources & evidence

ORD record
ord-34e338a61d0d4c00bd78514dce62c970
Source dataset
uspto-grants-2004_03
Patent number
US06713478B2

Reaction notes

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