Hydrochloric Acid → 2-amino-N-(3-bromo-2-methylphenyl)-3-methoxybenzamide

HRID 523217Notes

Reaction equation

HRID 523217 reaction equation
[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH3:10][O:11][C:12]1[C:17]2[NH:18]C(=O)[O:20][C:21](=O)[C:16]=2[CH:15]=[CH:14][CH:13]=1.C[Al](C)C.Cl>C1(C)C=CC=CC=1>[NH2:18][C:17]1[C:12]([O:11][CH3:10])=[CH:13][CH:14]=[CH:15][C:16]=1[C:21]([NH:5][C:4]1[CH:6]=[CH:7][CH:8]=[C:2]([Br:1])[C:3]=1[CH3:9])=[O:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1235383-Bromo-o-toluidineHCID 105596798-Methoxy-1H-benzo[d][1,3]oxazine-2,4-dioneHCID 16682925Trimethylaluminum

Product 1

HCID 1076239642-amino-N-(3-bromo-2-methylphenyl)-3-methoxybenzamideYield 35%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A mixture of 3-bromo-2-methylaniline (482 mg, 2.59 mmol) and 8-methoxy-1H-benzo[d][1,3]oxazine-2,4-dione (500 mg, 2.59 mmol) in toluene (20 mL) was treated with 2 M trimethylaluminum in toluene (3.24 mL, 6.47 mmol) at 0° C. The mixture was stirred at room temperature for 10 minutes, then was heated at 70° C. overnight. The mixture was cooled to room temperature, treated with 1N aqueous HCl and extracted 3 times with EtOAc. The combined organic phases were washed sequentially with saturated aqueous NaHCO3 and water, dried and concentrated. The residue was subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexanes (gradient from 0-100%), to provide 2-amino-N-(3-bromo-2-methylphenyl)-3-methoxybenzamide as a white solid (302 mg, 35% yield). Mass spectrum m/z 335, 337 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 7.72 (d, J=7.3 Hz, 2H), 7.46 (dd, J=8.0, 0.8 Hz, 1H), 7.17-7.10 (m, 2H), 6.90 (dd, J=7.9, 0.9 Hz, 1H), 6.72-6.66 (m, 1H), 5.88 (br. s., 2H), 3.92 (s, 3H), 2.43 (s, 3H).

Workup

  1. temperaturewas heated at 70° C. overnight
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted 3 times with EtOAc
  4. washThe combined organic phases were washed sequentially with saturated aqueous NaHCO3 and water
  5. customdried
  6. concentrationconcentrated
  7. washeluting with EtOAc-hexanes (gradient from 0-100%)

Sources & evidence

ORD record
ord-c5b7b2f8b5fa4f8fa49c868b34b1cf39
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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