Reaktion #2507878

Reaktionsgleichung

2-chloro-5-nitropyridine

DMF

N-(2-hydroxyethyl)pyrrolidine

NaH

→

5-amino-2-((pyrrolidin-1-yl)ethoxy)pyridine

Lösungsmittel

H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGAfter stirring overnight
2. 2
   Extraktionextracted 3× with EtOAc
3. 3
   WaschenThe combined organic layers were washed 2× with H2O
4. 4
   Trocknento drying over Na2SO4, Concentration under vacuum
5. 5
   Sonstigeyielded an orange oil which
6. 6
   Sonstigewas chromatographed on silica gel employing ˜10% MeOH/CH2Cl2
7. 7
   Waschento elute 1.62 g of 5-nitro-2-(pyrrolidin-1-yl)-ethoxy)pyridine (54%)
8. 8
   workup.ADDITIONcontaining 10% Pd/C (0.1 g) under 60 psi of H2 for 4 hr
9. 9
   FiltrationUpon completion the reaction was filtered
10. 10
    Einengento concentration under vacuum
11. 11
    SonstigeThe resulting dark oil was chromatographed on silica
12. 12
    WaschenGradient elution (CH2CL2 to 20% MeOH/CH2Cl2)
13. 13
    Wascheneluted 1.03 g of the title compound as a broad peak

Vorschrift

To a stirred DMF solution (25 mL) containing N-(2-hydroxyethyl)pyrrolidine (2.18 g, 18.9 mmol) under N2 was added 60% NaH in mineral oil (0.76 g, 18.9 mmol). The mixture was stirred for 1 hr while gas evolution ceased. Subsequently 2-chloro-5-nitropyridine (2.0 g, 12.6 mmol) was added. After stirring overnight, the dark solution was poured into H2O (100 mL) and extracted 3× with EtOAc. The combined organic layers were washed 2× with H2O prior to drying over Na2SO4, Concentration under vacuum yielded an orange oil which was chromatographed on silica gel employing ˜10% MeOH/CH2Cl2 to elute 1.62 g of 5-nitro-2-(pyrrolidin-1-yl)-ethoxy)pyridine (54%). The above product reduced, to the corresponding substituted aminopyridine by hydrogenation in an EtOH solution (20 mL) containing 10% Pd/C (0.1 g) under 60 psi of H2 for 4 hr. Upon completion the reaction was filtered prior to concentration under vacuum. The resulting dark oil was chromatographed on silica. Gradient elution (CH2CL2 to 20% MeOH/CH2Cl2) eluted 1.03 g of the title compound as a broad peak.

Quelle