Réaction #76791

Équation de réaction

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

Rendement 64.0%

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

Rendement 64.0%

Solvants

methanol

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGstirred for 16 hours
2. 2
   Températureheated
3. 3
   Températureat reflux for 1 hour
4. 4
   Températureat reflux for 2 hours more
5. 5
   AutreThe solvent was evaporated under reduced pressure
6. 6
   Autrethe residue was partitioned between water (1 mL) and chloroform (4 mL)
7. 7
   Autreseparated
8. 8
   Extractionextracted the aqueous phase with chloroform (2×4 mL)
9. 9
   LavageThe combined organic layers were washed with brine (1 mL)
10. 10
    Séchagedried (MgSO4)
11. 11
    Autreevaporated under reduced pressure
12. 12
    Autrepurified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5)

Mode opératoire

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).

Source