反応 #76791

反応方程式

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

収率 64.0%

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

収率 64.0%

溶媒

methanol

反応条件

後処理

1. 1
   workup.STIRRINGstirred for 16 hours
2. 2
   温度heated
3. 3
   温度at reflux for 1 hour
4. 4
   温度at reflux for 2 hours more
5. 5
   その他The solvent was evaporated under reduced pressure
6. 6
   その他the residue was partitioned between water (1 mL) and chloroform (4 mL)
7. 7
   その他separated
8. 8
   抽出extracted the aqueous phase with chloroform (2×4 mL)
9. 9
   洗浄The combined organic layers were washed with brine (1 mL)
10. 10
    乾燥dried (MgSO4)
11. 11
    その他evaporated under reduced pressure
12. 12
    その他purified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5)

実験手順

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).

出典