Phosphorus oxychloride → 2-Chloro-6-fluoroimidazo[1,2-A]pyridine
Reaction equation
Br.[NH:2]=[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][N:4]1[CH2:10][C:11](OCC)=O.P(Cl)(Cl)([Cl:18])=O>>[Cl:18][C:11]1[N:2]=[C:3]2[CH:8]=[CH:7][C:6]([F:9])=[CH:5][N:4]2[CH:10]=1Participants
3
Conditions
- Temperature
- 105 °C
Procedure
A mixture of ethyl 2-imino-5-fluoro-1,2-dihydropyridine-1-yl-acetate hydrobromide (4.12 g, 14.76 mmol) in phosphorus oxychloride (68.8 mL, 738 mmol) was heated at 105° C. for 2 hours. The mixture was then cooled to room temperature and concentrated under reduced pressure. To the resulting residue were added ice water and ammonium hydroxide until the pH of the solution was 8. The solution was then extracted with dichloromethane. The organic extracts were combined, dried over MgSO4, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (30% ethyl acetate in hexanes) provided the title compound: LCMS m/z 170.96 [M+H]+, 172.79 [M+2+H]+; 1H NMR (500 MHz, CDCl3) δ 8.00 (s, 1H), 7.53-7.50 (m, 2H), 7.18-7.13 (m, 1H).