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

HRID 470652Notes

Reaction equation

HRID 470652 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[CH2:25][CH2:24][CH2:23][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)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

4

Reactant 2

HCID 168483',4'-Dimethoxycinnamic acidHCID 178513282N'-hydroxycyclohexanecarboximidamide2×

Product 1

HCID 673959833-Cyclohexyl-5-[2-(3,4-dimethoxy-phenyl)-vinyl]-[1,2,4]oxadiazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

To a solution of 1.43 g (6.9 mmol) of 3-(3,4-dimethoxy-phenyl)-acrylic acid (compound of Example 2; Step 1) in 22 mL of toluene, 1.21 g (7.5 mmol) of 1,1-carbonyldiimidazole was added in portions at 25° C. to 30° C. under inert atmosphere. To the thickened mixture, 22 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-hydroxycyclohexanecarboximidamide (compound of Example 59; 2 g, 14 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-2b0a49caf0e443eba123230d68864d7b
Source dataset
uspto-grants-2014_01
Patent number
US08629277B2

Reaction notes

Loading…