Phosphorus oxychloride → 3-(2-(3-Chlorophenyl)ethyl)-2-pyridinecarbonitrile
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]=1Participants
Procedure
A solution of 3-[2-(3-chlorophenyl)ethyl]-N-(1,1-dimethylethyl)-2-pyridine carboxamide (175 g, 0.554 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
- temperatureat reflux for 3 hours
- customExcess phosphorous oxychloride is removed by distillation at reduced pressure
- customthe residue is quenched into a mixture of water and isopropanol
- additionThe pH is brought to 5-7 by addition of 50% aqueous sodium hydroxide solution
- temperaturewhile maintaining the temperature below 30° C
- filtrationThe crystalline slurry of crude product is filtered
- washwashed with water
- customCrude product is purified
- temperatureby cooling at 0°-5° C
- filtrationThe product is filtered
- washwashed with hexane
- customdried at below 50° C
Sources & evidence
- ORD record
- ord-5e2cb32d6bd6492593450495a2bbeedb
- Source dataset
- uspto-grants-1987_04
- Patent number
- US04659716
Reaction notes
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