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; 0.55 mol) in 525 mL (5.6 mol) of phosphorous oxychloride was heated at reflux for 3 h. Excess phosphorus oxychloride (-300 mL) was removed by distillation and the remaining solution was carefully poured into ice-water. The pH of the solution was adjusted to 8 with 50% aqueous sodium hydroxide while the temperature was maintained at 25°-30° C. The mixture was stirred for 2h during which time the pH was maintained at 8. The product was collected by filtration, washed with water and dried in a vacuum oven at 50° C. to give 127 g (95%) of crystalline 3-[2-(3chlorophenyl)ethyl]-2-pyridinecarbonitrile: m.p. 72°-73° C.; NMR (200 MHz, CDCl3)δ2.9-3.1 (m,2H), 3.1-3.2 (m,2H), 7.0-7.1 (m,1H), 7.1- 7.3 (m,3H), 7.42 (dd,1H,J=7.3, 5 Hz); 7.56 (dd,1H,J=7.3, 1.2 Hz), 8.48 (dd,J=5, 1.2 Hz); mass spectrum, m/e (rel intensity) 242 M+ (18). Anal. Calcd for C14H11N2Cl: C,69.28; H,4.59; N,11.54; Cl 14.61. Found: C,69.37; H,4.48; N,ll.39; Cl,14.48.
Workup
- temperatureat reflux for 3 h
- customExcess phosphorus oxychloride (-300 mL) was removed by distillation
- additionthe remaining solution was carefully poured into ice-water
- temperaturewas maintained at 25°-30° C
- temperaturewas maintained at 8
- filtrationThe product was collected by filtration
- washwashed with water
- customdried in a vacuum oven at 50° C.
Sources & evidence
- ORD record
- ord-a3194b9539c44701a519d432735a30c6
- Source dataset
- uspto-grants-1989_09
- Patent number
- US04863931
Reaction notes
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