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

HRID 49610Notes

Reaction equation

HRID 49610 reaction equation
[Na].[NH2:2][C:3]1[CH:4]=[C:5]2[CH2:11][C:10]3([CH:16]4[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]4)[CH2:12]3)[O:9][C:6]2=[N:7][CH:8]=1.[CH2:19]=O.[BH4-].[Na+].[OH-].[K+]>CO>[CH3:19][NH:2][C:3]1[CH:4]=[C:5]2[CH2:11][C:10]3([CH:16]4[CH2:15][CH2:14][N:13]([CH2:18][CH2:17]4)[CH2:12]3)[O:9][C:6]2=[N:7][CH:8]=1

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 14797Potassium HydroxideHCID 4311764Sodium borohydrideHCID 5360545SodiumHCID 15908236spiro[1-azabicyclo[2.2.2]octane-3,2'-3H-furo[2,3-b]pyridine]-5'-amine

Product 1

HCID 159082385'-(N-Methylamino)spiro[1-azabicyclo[2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine]Yield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

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).

Workup

  1. stirringstirred for 16 hours
  2. temperatureheated
  3. temperatureat reflux for 1 hour
  4. temperatureat reflux for 2 hours more
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was partitioned between water (1 mL) and chloroform (4 mL)
  7. customseparated
  8. extractionextracted the aqueous phase with chloroform (2×4 mL)
  9. washThe combined organic layers were washed with brine (1 mL)
  10. dry with materialdried (MgSO4)
  11. customevaporated under reduced pressure
  12. custompurified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5)

Sources & evidence

ORD record
ord-8abe23a653e14a609e36a443dabc6357
Source dataset
uspto-grants-2004_03
Patent number
US06706878B2

Reaction notes

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