Phosgene → 5-Methoxy-2H-3,1-benzoxazine-2,4(1H)-dione

HRID 1045942Notes

Reaction equation

[C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[C:7]=1[C:8]([OH:10])=[O:9].[OH-].[Na+]>O>[CH3:16][O:15][C:11]1[C:7]2[C:8](=[O:10])[O:9][C:1](=[O:2])[NH:5][C:6]=2[CH:14]=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 0 °C

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

temperaturemaintaining the temperature at 0-5° C
filtrationThe precipitate was collected by filtration
washwashed with water
customdried under vacuum at 40° C.

Sources & evidence

ORD record: ord-f2fc583b38fd4452815e9192b938d5d7
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569298B2

Reaction notes

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