تفاعل #168230

معادلة التفاعل

Sodium nitrite

2-amino-3,5-dichloroisonicotinonitrile

tetrafluoroboric acid

→

3,5-dichloro-2-fluoroisonicotinonitrile

المردود 36.5%

ظروف التفاعل

المعالجة

1. 1
   أخرىcarefully quenched with ice and solid Na2CO3
2. 2
   استخلاصextracted with ethyl acetate (3×150 mL)
3. 3
   غسيلThe combined organic layers were washed with brine (100 mL)
4. 4
   تجفيفdried (MgSO4)
5. 5
   تركيزconcentrated to ˜20 mL in volume
6. 6
   أخرىtriturated with dichloromethane (30 mL)
7. 7
   ترشيحfiltered
8. 8
   تركيزThe filtrate was concentrated
9. 9
   أخرىpurified by silica gel chromatography
10. 10
    غسيلeluting with 5 to 30% ethyl acetate in hexanes

الإجراء التجريبي

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).

المصدر