3-Cyclobutene-1,2-dione, 3,4-dimethoxy- → 3-[2-Hydroxy-3-(morpholine-4-carbonyl)phenylamino]-4-methoxycyclobut-3-ene-1,2-dione
Reaction equation
[NH2:1][C:2]1[C:3]([OH:16])=[C:4]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:17][O:18][C:19]1[C:20](=O)[C:21](=[O:25])[C:22]=1[O:23]C>CO>[OH:16][C:3]1[C:4]([C:8]([N:10]2[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)=[O:9])=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:20]1[C:21](=[O:25])[C:22](=[O:23])[C:19]=1[O:18][CH3:17]Participants
4
Procedure
A solution of 1.00 g (4.5 mmol) of (3-amino-2-hydroxyphenyl)morpholin-4-ylmethanone and 2.56 g (18.0 mmol) of 3,4-dimethoxycyclobut-3-ene-1,2-dione in 100 ml of methanol was heated at 50° C. for five and a half hours. The reaction medium was concentrated. The residue was taken up in ethyl acetate and was washed twice with a 1 M aqueous sodium dihydrogen phosphate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The solvent was evaporated off and the residue was chromatographed on silica gel (200 g prepacked column, eluent dichloromethane/methanol from 0 to 5% of methanol). 0.81 g of a yellow solid was obtained (dirty fraction). This solid was taken up in methanol with stirring, filtered and rinsed with methanol. 0.50 g of product was obtained in the form of a pale yellow solid. Yield=33%.