Reacción #465960

Ecuación de reacción

Sodium azide

methyl 3-chloro-4,6-difluoropyridine-2-carboxylate

water

→

methyl 4-amino-3-chloro-6-fluoropyridine-2-carboxylate

Rendimiento 81.9%

Disolventes

dimethyl formamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracting the aqueous mixture with EtOAc (2×100 mL)
2. 2
   SecadoThe organic phase was dried (Na2SO4)
3. 3
   workup.ADDITIONtreated with excess NaBH4 for 30 min
4. 4
   OtroThe excess NaBH4 was quenched with aqueous EtOH
5. 5
   workup.ADDITIONthe mixture was diluted with water (200 mL)
6. 6
   OtroThe organic layer was separated
7. 7
   Extracciónthe aqueous layer extracted with EtOAc (2×200 mL)
8. 8
   SecadoThe combined organic layers were dried (Na2SO4)
9. 9
   Concentraciónconcentrated to an off-white powder which
10. 10
    Otrowas purified by reversed-phase HPLC

Procedimiento

Sodium azide (0.0086 mol, 0.60 g) was added to a solution of methyl 3-chloro-4,6-difluoropyridine-2-carboxylate (0.0072 mol, 1.5 g) in 15 mL dimethyl formamide (DMF). The solution was stirred 10 min at ambient temperature before pouring into 350 mL water and extracting the aqueous mixture with EtOAc (2×100 mL). The organic phase was dried (Na2SO4) and then treated with excess NaBH4 for 30 min. The excess NaBH4 was quenched with aqueous EtOH and the mixture was diluted with water (200 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (2×200 mL). The combined organic layers were dried (Na2SO4) and concentrated to an off-white powder which was purified by reversed-phase HPLC to give methyl 4-amino-3-chloro-6-fluoropyridine-2-carboxylate (0.0059 mol, 1.2 g). 1H NMR(CDCl3): δ 3.95 (3H, s), 5.2-5.1 (2H, bs), 6.36 (1H, s). 19F NMR {1H}: δ −72.7.

Fuente