Phosphorus oxychloride → 6-Fluoroimidazo[1,5-A]pyridine
Reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][NH:9][CH:10]=O)=[N:6][CH:7]=1.P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:10]=[N:9][CH:8]=2)[CH:7]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
In a round-bottomed flask, N-(5-fluoro-pyridin-2-ylmethyl)-formamide (612 mg, 3.97 mmol) was dissolved in toluene (16 ml) and phosphorus oxychloride (0.68 ml, 7.3 mmol) was added. The reaction mixture was stirred at 100° C. in an oil bath for 4 h then cooled to 0° C. and carefully quenched with ice. Aqueous 25% ammonium hydroxide was added until pH=˜9. The mixture was diluted with water and extracted with dichloromethane (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated to give 517 mg (96%) of 6-fluoro-imidazo[1,5-a]pyridine as a light brown oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.16 (s, 1H), 7.84-7.94 (m, 1H), 7.50 (s, 1H), 7.46 (dd, J=9.8, 5.3 Hz, 1H), 6.69 (ddd, J=9.8, 7.7, 2.1 Hz, 1H).