Phosphorus oxychloride → HCID 178426119, compound

Temperature

40 °C

To a solution of 2,4-dihydroxy-6-methylnicotinonitrile (1.5 g, 10 mmol) in acetonitrile (50 mL) were added benzyltriethylammonium chloride (9.1 g, 40 mmol) and phosphoryl chloride (6.13 g, 40 mmol). The reaction mixture was heated to 40° C. for 4 hours at the same temperature. LC-MS showed that 2,4-dihydroxy-6-methylnicotinonitrile was consumed completely. The solvent was removed by rotary evaporation. To the residue was added dichloromethane (100 ml) and water (50 ml). The organic phase was separated, and it was washed with brine (50 ml) once, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give crude product which was purified by silica gel column chromatography with dichloromethane/methanol=10:1 to afford 4-chloro-2-hydroxy-6-methylnicotinonitrile (800 mg, 24% yield) as a brown solid.

1. customwas consumed completely
2. customThe solvent was removed by rotary evaporation
3. additionTo the residue was added dichloromethane (100 ml) and water (50 ml)
4. customThe organic phase was separated
5. washit was washed with brine (50 ml) once
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give crude product which
10. customwas purified by silica gel column chromatography with dichloromethane/methanol=10:1

ORD record

ord-25a01f167ca74c5099b64e0e2fc0c405

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206128B2