Reaktion #76791

Reaktionsgleichung

sodium borohydride

5′-Aminospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine]

paraformaldehyde

sodium

potassium hydroxide

→

title compound

Ausbeute 64.0%

5′-(N-Methylamino)spiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine]

Ausbeute 64.0%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 16 hours
2. 2
   Temperaturheated
3. 3
   Temperaturat reflux for 1 hour
4. 4
   Temperaturat reflux for 2 hours more
5. 5
   SonstigeThe solvent was evaporated under reduced pressure
6. 6
   Sonstigethe residue was partitioned between water (1 mL) and chloroform (4 mL)
7. 7
   Sonstigeseparated
8. 8
   Extraktionextracted the aqueous phase with chloroform (2×4 mL)
9. 9
   WaschenThe combined organic layers were washed with brine (1 mL)
10. 10
    Trocknendried (MgSO4)
11. 11
    Sonstigeevaporated under reduced pressure
12. 12
    Sonstigepurified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5)

Vorschrift

Under a nitrogen atmosphere, sodium (50 mg, 2.17 mmol) was slowly added (exothermic) to methanol (1 mL) and stirred for 1 hour. 5′-Aminospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (115 mg, 0.5 mmol) and paraformaldehyde (35 mg, 1.17 mmol) were added and stirred for 16 hours. The reaction was heated at 50° C. for 4 hours, sodium borohydride (53 mg, 1.4 mmol) was added, and heated at reflux for 1 hour. Then, 1 N aqueous potassium hydroxide (0.4 mL) was added and continued at reflux for 2 hours more. The solvent was evaporated under reduced pressure, the residue was partitioned between water (1 mL) and chloroform (4 mL), separated and extracted the aqueous phase with chloroform (2×4 mL). The combined organic layers were washed with brine (1 mL), dried (MgSO4), evaporated under reduced pressure, and purified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5) to obtain the title compound (78 mg, 0.32 mmol, 64%) as an off-white solid: electrospray MS (m/z, relative intensity) 246 ([MH]+, 100).

Quelle