3-Cyclobutene-1,2-dione, 3,4-dimethoxy- → 3-[2-Hydroxy-3-(morpholine-4-carbonyl)phenylamino]-4-methoxycyclobut-3-ene-1,2-dione

HRID 1528174Notes

Reaction equation

HRID 1528174 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

Reactant 2

HCID 1232273-Cyclobutene-1,2-dione, 3,4-dimethoxy-HCID 12404608(3-Amino-2-hydroxyphenyl)(morpholino)methanone

Product 1

HCID 895263243-[2-Hydroxy-3-(morpholine-4-carbonyl)phenylamino]-4-methoxycyclobut-3-ene-1,2-dioneYield 54.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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%.

Workup

  1. concentrationThe reaction medium was concentrated
  2. washwas washed twice with a 1 M aqueous sodium dihydrogen phosphate solution
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe solvent was evaporated off
  7. customthe residue was chromatographed on silica gel (200 g prepacked column, eluent dichloromethane/methanol from 0 to 5% of methanol)

Sources & evidence

ORD record
ord-2cb69d1a583d4a68b1ae35e5b5b33ffb
Source dataset
uspto-grants-2015_07
Patent number
US09090596B2

Reaction notes

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