Methylamine → 2-amino-6-methoxy-N-methylbenzamide

HRID 1045943Notes

Reaction equation

HRID 1045943 reaction equation
[CH3:1][NH2:2].[CH3:3][O:4][C:5]1[C:10]2[C:11](=O)[O:12]C(=O)[NH:14][C:9]=2[CH:8]=[CH:7][CH:6]=1>O.CCOC(C)=O>[NH2:14][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]([O:4][CH3:3])[C:10]=1[C:11]([NH:2][CH3:1])=[O:12]

Participants

5

Reactant 2

HCID 6329MethylamineHCID 107502955-Methoxy-2H-3,1-benzoxazine-2,4(1H)-dione

Product 1

HCID 122648202-amino-6-methoxy-N-methylbenzamideYield 70.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phosgene (4.72 ml, 8.97 mmol; 20% in toluene) was added dropwise to a solution of 2-amino-6-methoxybenzoic acid (1 g, 5.98 mmol) in 2N aqueous sodium hydroxide (6.28 ml, 12.56 mmol) and water (15 ml) cooled to 0° C. over a period of 15 minutes, maintaining the temperature at 0-5° C. The resulting suspension was stirred at 0° C. for 15 minutes. The precipitate was collected by filtration, washed with water, followed by a small amount of acetonitrile and ether and dried under vacuum at 40° C. to afford 5-methoxy-1H-3,1-benzoxazine-2,4-dione (0.760 g, 65.8%) as a beige solid. 40% aqueous methylamine (1.57 ml, 18.1 mmol) was added to a stirred suspension of 5-methoxy-1H-3,1-benzoxazine-2,4-dione (700 mg, 3.62 mmol;) in water (5 ml). The resulting solution was stirred at room temperature for 36 hours. The mixture was diluted with EtOAc, washed sequentially with saturated aqueous sodium carbonate, water and brine. The organic layer was dried over MgSO4 and evaporated to afford 2-amino-6-methoxy-N-methylbenzamide (457 mg, 70.0%) as a white solid. 1H NMR spectrum (500 MHz, DMSO): 2.73 (d, 3H), 3.73 (s, 3H), 5.79 (bs, 2H), 6.19 (d, 1H), 6.30 (d, 1H), 6.99 (dd, 1H), 7.98 (q, 1H).

Workup

  1. washwashed sequentially with saturated aqueous sodium carbonate, water and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. customevaporated

Sources & evidence

ORD record
ord-03d6786665f4427db762b92fa61850e7
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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