Tetrafluoroboric acid → 3,5-Dichloro-2-fluoroisonicotinonitrile

Sodium nitrite (3.17 g, 46.0 mmol) was added in small portions to a suspension of crude 2-amino-3,5-dichloroisonicotinonitrile (4.32 g) in tetrafluoroboric acid (60 mL, 806 mmol) at −10° C. over 1 h. The resultant mixture was stirred at −10° C. for 1 h, carefully quenched with ice and solid Na2CO3 and extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine (100 mL), dried (MgSO4), concentrated to ˜20 mL in volume, triturated with dichloromethane (30 mL) and filtered. The filtrate was concentrated and purified by silica gel chromatography, loading with dichloromethane-hexanes (1:1) and eluting with 5 to 30% ethyl acetate in hexanes, to give 3,5-dichloro-2-fluoroisonicotinonitrile (1.60 g, 36% yield for 2 steps). 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (1H, s); LC retention time: 2.758 min (analytical HPLC Method A).

1. customcarefully quenched with ice and solid Na2CO3
2. extractionextracted with ethyl acetate (3×150 mL)
3. washThe combined organic layers were washed with brine (100 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated to ˜20 mL in volume
6. customtriturated with dichloromethane (30 mL)
7. filtrationfiltered
8. concentrationThe filtrate was concentrated
9. custompurified by silica gel chromatography
10. washeluting with 5 to 30% ethyl acetate in hexanes

ORD record

ord-3891f799e54142688f268e9e451cacdd

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846673B2