反应 #465960

反应方程式

Sodium azide

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

water

→

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

收率 81.9%

溶剂

dimethyl formamide

反应条件

后处理

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

实验过程

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.

来源