تفاعل #465960

معادلة التفاعل

Sodium azide

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

water

→

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

المردود 81.9%

المذيبات

dimethyl formamide

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر