Ethanol → 1,4-Dimethyl 2-[(2-bromo-4-methoxyphenyl)amino]-2-butenedioate

HRID 1795334Notes

Reaction equation

HRID 1795334 reaction equation
[Br:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[C:11]([C:17]([O:19][CH3:20])=[O:18])#[C:12][C:13]([O:15][CH3:16])=[O:14].C(O)C>CO>[CH3:16][O:15][C:13](=[O:14])[C:12]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:2]=1[Br:1])=[CH:11][C:17]([O:19][CH3:20])=[O:18]

Participants

5

Reactant 3

HCID 702EthanolHCID 12980Dimethyl acetylenedicarboxylateHCID 108996712-Bromo-4-methoxyaniline

Product 1

HCID 692678581,4-Dimethyl 2-[(2-bromo-4-methoxyphenyl)amino]-2-butenedioateYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-bromo-4-methoxy aniline (6.02 g, 29.8 mmol) in 125 mL anhydrous methanol was treated with dimethyl acetylenedicarboxylate (3.70 mL, 30.2 mmol) and the solution was heated at reflux under nitrogen for 8 hours. The reaction mixture was cooled, concentrated, and redissolved in hot methanol. Yellow crystals were obtained by filtration (6.93 g, 68%). A second crop of crystals was obtained from ethanol (0.942 g, 9%). The filtrates were combined and purified by flash chromatography on silica gel using 4:1 hexanes:ethyl acetate to afford an additional 1.63 g (16%) for a total yield of 93%. 1H NMR (300 MHz, DMSO, d6) δ 9.60 (s, 1 H, NH), 7.26 (d, 1 H, Jm=2.7 Hz, ArH3), 6.93 (dd, 1 H, Jo=8.7, Jm=2.7 Hz, ArH5), 6.87 (d, 1 H, Jo=8.7 Hz, ArH6), 5.34 (s, 1 H, C═CH), 3.76 (s, 3H, OCH3), 3.68 (s, 3 H, CHCO2CH3), 3.66 (s, 3 H, CNCO2CH3); Mass Spec.: calc. for [C13H14BrNO5+H]+ Theor. m/z=344, 346; Obs. 344, 346.

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux under nitrogen for 8 hours
  3. temperatureThe reaction mixture was cooled
  4. concentrationconcentrated
  5. dissolutionredissolved in hot methanol
  6. customYellow crystals were obtained by filtration (6.93 g, 68%)
  7. custompurified by flash chromatography on silica gel using 4:1 hexanes
  8. customethyl acetate to afford an additional 1.63 g (16%) for a total yield of 93%

Sources & evidence

ORD record
ord-a4d14a719ee54a5782a9d38d74b4e9ca
Source dataset
uspto-grants-2006_04
Patent number
US07026314B2

Reaction notes

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