Phosphorus oxychloride → 6-Fluoroimidazo[1,5-A]pyridine

Temperature

100 °C

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).

1. temperaturethen cooled to 0° C.
2. customcarefully quenched with ice
3. additionAqueous 25% ammonium hydroxide was added until pH=˜9
4. additionThe mixture was diluted with water
5. extractionextracted with dichloromethane (3×)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-c3a2821918b145de94ff4b42882b74b3

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2