Water → 3-[3-(4-Fluorophenyl)-1-(1-methylethyl)-1H-indol-2-YL]-2-propenal

HRID 9938

Reaction equation

HRID 9938 reaction equation
[CH:1]([CH:3]=[CH2:4])=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([CH:21]([CH3:23])[CH3:22])[CH:13]=2)=[CH:8][CH:7]=1.P(Cl)(Cl)(Cl)=O.O>C(#N)C>[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([CH:21]([CH3:23])[CH3:22])[C:13]=2[CH:4]=[CH:3][CH:1]=[O:2])=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7847Acrolein2×HCID 24813Phosphorus oxychlorideHCID 7362293-(4-Fluorophenyl)-1-(1-methylethyl)-1H-indole

Product 1

HCID 533952913-[3-(4-Fluorophenyl)-1-(1-methylethyl)-1H-indol-2-YL]-2-propenal

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

Use of the crude acrolein coming from Example 4a. To a suspension of 3-[3-(4-Fluorophenyl)-1-(1-Methylethyl)-1H-Indole (130.7 g), phosphorus oxychloride (114.6 g) in acetonitrile (128 ml) cooled at 5° C. a solution of crude acrolein (116.9 g from Example 4a) in acetonitrile (145 ml) is added dropwise in 60 minutes. The reaction mixture is then warmed to 60° C. and kept under stirring at 60° C. for 6 hours; water (1100 ml) is added and after 1 hour at 60° C. the formed solid is filtered on Buchner and washed with water (250 ml×3). The wet solid (131 g) is dissolved in toluene (1050 ml), celite (2.7 g) and charcoal (4 g) are added and the mixture is stirred at room temperature for 30 minutes. After filtration of the solid, the mixture is washed with water (500 ml×2), the phases are separated, the organic solvent is distilled off at reduced pressure and the residue is dissolved at 75° C. with isopropanol (260 ml). The solution is cooled at 10° C. and stirred for 1 hour. The precipitate is filtered on Buchner, washed with isopropanol (60 ml×3) and dried at 60° C. under vacuum. 84.2 g (53% molar yield) of the product are obtained.

Workup

  1. additionis added dropwise in 60 minutes
  2. filtrationis filtered on Buchner
  3. washwashed with water (250 ml×3)
  4. dissolutionThe wet solid (131 g) is dissolved in toluene (1050 ml)
  5. additioncelite (2.7 g) and charcoal (4 g) are added
  6. stirringthe mixture is stirred at room temperature for 30 minutes
  7. filtrationAfter filtration of the solid
  8. washthe mixture is washed with water (500 ml×2)
  9. customthe phases are separated
  10. distillationthe organic solvent is distilled off at reduced pressure
  11. dissolutionthe residue is dissolved at 75° C. with isopropanol (260 ml)
  12. temperatureThe solution is cooled at 10° C.
  13. stirringstirred for 1 hour
  14. filtrationThe precipitate is filtered on Buchner
  15. washwashed with isopropanol (60 ml×3)
  16. customdried at 60° C. under vacuum
  17. custom84.2 g (53% molar yield) of the product
  18. customare obtained

Sources & evidence

ORD record
ord-3f435dfa66004070964eaa59ec28607f
Source dataset
uspto-grants-2006_08
Patent number
US07091382B2

Linked notes

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