반응 #76791

반응 방정식

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

수율 64.0%

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

수율 64.0%

용매

methanol

반응 조건

후처리

1. 1
   workup.STIRRINGstirred for 16 hours
2. 2
   온도heated
3. 3
   온도at reflux for 1 hour
4. 4
   온도at reflux for 2 hours more
5. 5
   기타The solvent was evaporated under reduced pressure
6. 6
   기타the residue was partitioned between water (1 mL) and chloroform (4 mL)
7. 7
   기타separated
8. 8
   추출extracted the aqueous phase with chloroform (2×4 mL)
9. 9
   세척The combined organic layers were washed with brine (1 mL)
10. 10
    건조dried (MgSO4)
11. 11
    기타evaporated under reduced pressure
12. 12
    기타purified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5)

실험 절차

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).

출처