Phosphorus oxychloride → HCID 23124897, compound

HRID 547974Notes

Reaction equation

HRID 547974 reaction equation
FC1C=CC(C2C3C(=CC=CC=3)N(C(C)C)C=2)=CC=1.P(Cl)(Cl)(Cl)=O.CO/C=C/C#N.C(=O)([O-])O.[Na+].[F:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[N:45]([CH:52]([CH3:54])[CH3:53])[C:44]=2[CH:55]=[CH:56][C:57]#[N:58])=[CH:39][CH:38]=1>ClCCl>[F:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[N:45]([CH:52]([CH3:53])[CH3:54])[C:44]=2/[CH:55]=[CH:56]/[C:57]#[N:58])=[CH:39][CH:38]=1

Participants

7

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 7362293-(4-Fluorophenyl)-1-(1-methylethyl)-1H-indoleHCID 532471360838-50-8HCID 67196878HCID 67196878, compound

Product 1

HCID 23124897HCID 23124897, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a solution prepared by dissolving 0.63 g of 3-(4-fluorophenyl)-1-isopropyl-1H-indole in 3 mL of dichloromethane was added dropwise 0.77 g of phosphorus oxychloride at an inner temperature of 0 to 10° C., then, 0.92 g of trans-3-methoxyacrylonitrile was added dropwise. Then, the mixture was stirred overnight at room temperature to cause a reaction, further, the mixture was reacted for 6 hours at the reflux temperature. After completion of the reaction, the reaction liquid was added into 100 mL of 5 wt % aqueous sodium hydrogen carbonate, and extracted with ethyl acetate three times. The resulting organic layers were combined and washed with water, then, dried with anhydrous magnesium sulfate. The magnesium sulfate was filtrated off, and the resulting filtrate was concentrated to obtain a concentrated residue containing 3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]acrylonitrile (trans-cis isomer mixture containing mainly trans isomer). The resulting concentrated residue was purified by silica gel column chromatography (developing liquid: n-heptane/ethyl acetate: 10/1 to 5/1) to obtain 0.34 g of trans-3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]acrylonitrile (yellow solid). Yield: 45%

Workup

  1. customInto a solution prepared
  2. customa reaction
  3. customfurther, the mixture was reacted for 6 hours at the reflux temperature
  4. customAfter completion of the reaction
  5. customthe reaction liquid
  6. extractionextracted with ethyl acetate three times
  7. washwashed with water
  8. dry with materialdried with anhydrous magnesium sulfate
  9. filtrationThe magnesium sulfate was filtrated off
  10. concentrationthe resulting filtrate was concentrated
  11. customto obtain a concentrated residue
  12. additioncontaining mainly trans isomer)
  13. customThe resulting concentrated residue was purified by silica gel column chromatography (developing liquid: n-heptane/ethyl acetate: 10/1 to 5/1)

Sources & evidence

ORD record
ord-ca7c8a9825c94531adc834798246583a
Source dataset
uspto-grants-2011_05
Patent number
US07939674B2

Reaction notes

Loading…