3',4'-Dimethoxycinnamic acid → HCID 2961547, compound

HRID 470648Notes

Reaction equation

HRID 470648 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]([OH:15])=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O[NH:17][C:18](=[NH:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]2[O:15][N:25]=[C:18]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

4

Reactant 2

HCID 168483',4'-Dimethoxycinnamic acidHCID 178513339HCID 178513339, compound2×

Product 1

HCID 2961547HCID 2961547, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

To a solution of 4.35 g (20.95 mmol) of 3-(3,4-dimethoxy-phenyl)-acrylic acid (compound of Example 2; Step 1) in 35 mL of toluene, 3.703 g (22.8 mmol) of 1,1-carbonyldiimidazole was added in portions at 25° C. to 30° C. under inert atmosphere. To the thickened mixture, 15 mL of toluene was added and the resulting mixture was stirred at 25° C. to 30° C. for 60 to 90 min. A solution of N-hydroxy-nicotinimidamide (compound of Example 53; 6 g, 43.7 mmol) in 5 mL of toluene was added to the above reaction mixture at 25° C. to 30° C. The reaction mixture was stirred at 25° C. to 30° C. under nitrogen for 12-14 h, followed by stirring at 100° C. to 105° C. for 6-8 h. After completion of the reaction, the reaction mixture was cooled to 25° C. to 30° C. and quenched with 10 mL of chilled water under stirring at 25° C. to 30° C. The organic layer was separated, and the aqueous layer was washed with 5 mL of toluene. The organic layers were combined and washed with 10 mL of 1N HCl solution, 10 mL of 5% sodium bicarbonate solution and 10 mL of 10% sodium chloride solution. The organic layer was distilled completely to obtain a crude residue, which was purified by column chromatography (silica gel, chloroform-methanol) to yield the title compound.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. to 30° C. under nitrogen for 12-14 h
  2. stirringby stirring at 100° C. to 105° C. for 6-8 h
  3. customAfter completion of the reaction
  4. temperaturethe reaction mixture was cooled to 25° C. to 30° C.
  5. customquenched with 10 mL of chilled water
  6. stirringunder stirring at 25° C. to 30° C
  7. customThe organic layer was separated
  8. washthe aqueous layer was washed with 5 mL of toluene
  9. washwashed with 10 mL of 1N HCl solution, 10 mL of 5% sodium bicarbonate solution and 10 mL of 10% sodium chloride solution
  10. distillationThe organic layer was distilled completely
  11. customto obtain a crude residue, which
  12. customwas purified by column chromatography (silica gel, chloroform-methanol)

Sources & evidence

ORD record
ord-7eacd19f26794f9a92b33b6271d3aee0
Source dataset
uspto-grants-2014_01
Patent number
US08629277B2

Reaction notes

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