3',4'-Dimethoxycinnamic acid → 3-Cyclopropyl-5-[2-(3,4-dimethoxy-phenyl)-vinyl]-[1,2,4]oxadiazole

HRID 470631Notes

Reaction equation

HRID 470631 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]([CH:20]1[CH2:22][CH2:21]1)=[NH:19]>C1(C)C=CC=CC=1>[CH:20]1([C:18]2[N:19]=[C:13]([CH:12]=[CH:11][C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[O:15][N:17]=2)[CH2:22][CH2:21]1

Participants

4

Reactant 2

HCID 168483',4'-Dimethoxycinnamic acidHCID 178513214HCID 178513214, compound2×

Product 1

HCID 673954903-Cyclopropyl-5-[2-(3,4-dimethoxy-phenyl)-vinyl]-[1,2,4]oxadiazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

To a solution of 2.74 g (13.2 mmol) of 3-(3,4-dimethoxy-phenyl)-acrylic acid (compound of Example 2; Step 1) in 20 mL of toluene, 2.18 g (13.4 mmol) of 1,1-carbonyldiimidazole was added in portions at 25° C. to 30° C. under inert atmosphere. To the thickened mixture, 5 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-cyclopropanecarboximidamide (compound of Example 35; 2.1 g, 26.9 mmol) in 10 mL of toluene was added to the above reaction mixture as one portion 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 20 mL of chilled water under stirring at 25° C. to 30° C. The organic layer was separated, and the aqueous layer was washed with 10 mL of toluene. The organic layers were combined and washed with 20 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 material, 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 20 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 10 mL of toluene
  9. washwashed with 20 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 material, which
  12. customwas purified by column chromatography (silica gel, chloroform-methanol)

Sources & evidence

ORD record
ord-280e2cc2d5384cffa7bd0c28c2517431
Source dataset
uspto-grants-2014_01
Patent number
US08629277B2

Reaction notes

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