Phosphorus oxychloride → 3-(2-(3-Chlorophenyl)ethyl)-2-pyridinecarbonitrile

HRID 569207Notes

Reaction equation

HRID 569207 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[C:11]([C:16]([NH:18]C(C)(C)C)=O)=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1.P(Cl)(Cl)(Cl)=O>>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[C:11]([C:16]#[N:18])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 141286953-(2-(3-Chlorophenyl)ethyl)-N-(1,1-dimethylethyl)-2-pyridinecarboxamide

Product 1

HCID 41232253-(2-(3-Chlorophenyl)ethyl)-2-pyridinecarbonitrile

Conditions

Temperature
2.5 °C

Procedure

A solution of 3-[2-(3-chlorophenyl)ethyl]-N-(1,1-dimethylethyl)-2-pyridine carboxamide (175 g, 0.544 mole), in 525 mL (863 g, 5.63 mole) of phosphorous oxychloride is heated at reflux for 3 hours. Completion of the reaction is determined by thin layer chromatography. Excess phosphorous oxychloride is removed by distillation at reduced pressure and the residue is quenched into a mixture of water and isopropanol. The pH is brought to 5-7 by addition of 50% aqueous sodium hydroxide solution while maintaining the temperature below 30° C. The crystalline slurry of crude product is filtered and washed with water. Crude product is purified by slurrying the wet cake in hot isopropanol followed by cooling at 0-5° C. The product is filtered, washed with hexane and dried at below 50° C. Yield: 118 g (HPLC purity 95.7%), m.p. 72°-73° C., 89.4% of theory.

Workup

  1. temperatureat reflux for 3 hours
  2. customExcess phosphorous oxychloride is removed by distillation at reduced pressure
  3. customthe residue is quenched into a mixture of water and isopropanol
  4. additionThe pH is brought to 5-7 by addition of 50% aqueous sodium hydroxide solution
  5. temperaturewhile maintaining the temperature below 30° C
  6. filtrationThe crystalline slurry of crude product is filtered
  7. washwashed with water
  8. customCrude product is purified
  9. filtrationThe product is filtered
  10. washwashed with hexane
  11. customdried at below 50° C

Sources & evidence

ORD record
ord-ea58cfbcd1d24f6aab8ff4941d8bbd9c
Source dataset
uspto-grants-1988_03
Patent number
US04731447

Reaction notes

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