Phosphorus oxychloride → 6-Fluoro-3-methylimidazo[1,5-A]pyridine

Temperature

100 °C

In a round-bottomed flask, N-(5-fluoro-pyridin-2-ylmethyl)-acetamide (653 mg, 3.88 mmol) was dissolved in toluene (19 ml) and phosphorus oxychloride (0.66 ml, 7.1 mmol) was added. The reaction mixture was stirred at 100° C. in an oil bath overnight 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. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-70% EtOAc) to give 255 mg (44%) of 6-fluoro-3-methyl-imidazo[1,5-a]pyridine as a yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.61 (d, J=5.3 Hz, 1H), 7.38-7.50 (m, 2H), 6.67 (ddd, J=9.7, 7.6, 1.9 Hz, 1H), 2.66 (s, 3H).

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
9. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-70% EtOAc)

ORD record

ord-fc2afe2fcb4a48ec8eea61c72bda02a5

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2