Diethyl Ether → 3-(2-Pyrazinyl)-1-azabicyclo[2.2.2]octan-3-ol

HRID 256869Notes

Reaction equation

HRID 256869 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[CH2:20][CH2:19][CH:16]([CH2:17][CH2:18]1)[CH2:15][C:14]2=O.CC[O:24]CC>CCCCCC>[N:8]1[CH:9]=[CH:10][N:11]=[CH:12][C:7]=1[C:15]1([OH:24])[CH:16]2[CH2:19][CH2:20][N:13]([CH2:18][CH2:17]2)[CH2:14]1

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 5661191-azabicyclo[2.2.2]octan-2-oneHCID 642841IodopyrazineHCID 178418306HCID 178418306, compound

Product 1

HCID 157501353-(2-Pyrazinyl)-1-azabicyclo[2.2.2]octan-3-ol

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

t-Butyllithium (11.43 ml of a 1.4M solution in hexane, 16 mmol) was added dropwise to a rapidly stirred solution of 2-iodopyrazine (Hirschberg et al. J. Org. Chem., (1961), 26, 1907: 1.65 g, 8.0 mmol) in ether (60 ml). at -35° C. After 0.25 h a solution of quinuclidinone (1 g, 8.0 mmol) in ether (20 ml) was added dropwise and the reaction mixture warmed to room temperature and stirred for 2 h. Quenching with water (25 ml) was followed by extracting with dichloromethane (4×75 ml) and drying (Na2SO4). The residue remaining after evaporation of the solvents under reduced pressure was purified by chromatography on alumina (Grade II-III), using dichloromethane/methanol (93:7) as eluant, to give 3-(2-pyrazinyl)-1-azabicyclo[2.2.2]octan-3-ol as a red solid (0.5 g). The product was further purified by recrystallisation from ethyl acetate, m.p. 187°-190° C. (dec); (Found C, 64.24; H, 7.34; N, 20.68. C11H15N3O requires C, 64.39; H, 7.32: N, 20.49%); δ (360 MHz, CDCl3) 1.20-1.40 (1H m, CH of CH2); 1.50-1.70 (2H, m, CH2); 2.10-2.25 (1H, m, CH of CH2): 2.34 (1H, b rs, CH); 2.70-2.80 (2H, m, CH2 --N); 2.88-3.00 (3H, m, CH2 --N and CH of CH2 --N); 3.85 (1H, dd, J=1.5 and 16 Hz, CH of CH2 --N); 4.85 (1H, br s, OH); 8.54 (1H, d, J=2 Hz, pyrazine-H); 8.65 (1H, d, J=2 Hz, pyrazine-H); 8.89 (1H, d, J=2 Hz, pyrazine-H).

Workup

  1. customat -35° C
  2. customQuenching with water (25 ml)
  3. extractionby extracting with dichloromethane (4×75 ml)
  4. dry with materialdrying (Na2SO4)
  5. customafter evaporation of the solvents under reduced pressure
  6. customwas purified by chromatography on alumina (Grade II-III)

Sources & evidence

ORD record
ord-74bf2694b11f4b03ba17a46aec56886a
Source dataset
uspto-grants-1993_11
Patent number
US05260293

Reaction notes

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