Water → 3-(2-Pyrazinyl)-1-azabicyclo[2.2.1]heptan-3-ol

HRID 256874Notes

Reaction equation

HRID 256874 reaction equation
C([Li])(C)(C)C.I[C:7]1[CH:12]=[N:11][CH:10]=[CH:9][N:8]=1.[N:13]12[CH2:19][CH:16]([CH2:17][CH2:18]1)[C:15](=[O:20])[CH2:14]2.O>CCCCC.CCOCC.ClCCl>[N:8]1[CH:9]=[CH:10][N:11]=[CH:12][C:7]=1[C:15]1([OH:20])[CH:16]2[CH2:19][N:13]([CH2:18][CH2:17]2)[CH2:14]1

Participants

8

Reactant 4

HCID 962WaterHCID 642841IodopyrazineHCID 108554071-Azabicyclo[2.2.1]heptan-3-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 197841933-(2-Pyrazinyl)-1-azabicyclo[2.2.1]heptan-3-olYield 29.6%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolventHCID 8003PentaneSolvent

Procedure

t-Butyllithium (10.6 ml of a 1.7M solution in pentane, 18 mmol) was added dropwise to a rapidly stirred solution of 2-iodopyrazine (1.86 g, 9.0 mmol) in ether (50 ml), at -45° C. After 0.25 h a solution of 1-azabicyclo[2.2.1]heptan-3-one (1 g, 9.0 mmol) in ether (20 ml) was added dropwise and the reaction mixture warmed to room temperature and stirred for 16 h. Water (25 ml) was added and the solution stirred for 0.25 h before adding dichloromethane (150 ml) and extracting. The aqueous was extracted twice more with dichloromethane (2×150 ml). the extracts combined, dried (Na2SO4.MgSO4) and the solvent removed under vacuum. The residue was purified by chromatography through alumina, eluting with dichloromethane/methanol (93:7). Recrystallisation from ethyl acetate gave 3-(2-pyrazinyl)-1-azabicyclo[2.2.1]heptan-3-ol (0.51 g) as a pale yellow solid, m.p. 180°-183° C.; (Found C, 62.10; H,6.79; N,21.48. C10H13N3O.O.15 H2O requires C,61.95; H,6.87; N,21.68%; δ (360 MHz,CDCl3) 1.40-1.59(1H,m,CH of CH2); 2.33-2.36(1H,m,CH of CH2); 2.47(1H,dd,J=4 and 10 Hz, CH of CH2 --N); 2.59(1H,dd J=4 and 10 Hz, CH of CH2 --N); 2.74(1H,d, J=4Hz, CH-bridgehead); 2.76-2.81(1H,m,CH of CH2 --N); 2.93-3.03(2H,m,2×CH of 2×CH2 --N): 3.39(1H,dd J=1.5 and 15Hz, CH of CH2 --N); 4.10-4.30(1H,m,OH); 8.49-8.50(2H,m,pyrazine-H); 8.87(1H,m,pyrazine-H).

Workup

  1. stirringthe solution stirred for 0.25 h
  2. extractionextracting
  3. extractionThe aqueous was extracted twice more with dichloromethane (2×150 ml)
  4. dry with materialdried (Na2SO4.MgSO4)
  5. customthe solvent removed under vacuum
  6. customThe residue was purified by chromatography through alumina
  7. washeluting with dichloromethane/methanol (93:7)
  8. customRecrystallisation from ethyl acetate

Sources & evidence

ORD record
ord-f5094bafb7d4401ba34518f35540d688
Source dataset
uspto-grants-1993_11
Patent number
US05260293

Reaction notes

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