Water → 3-Fluoro-3-(2-pyrazinyl)-1-azabicyclo[2.2.1]heptane

HRID 256881Notes

Reaction equation

HRID 256881 reaction equation
C(N(S(F)(F)[F:7])CC)C.[N:10]1[CH:15]=[CH:14][N:13]=[CH:12][C:11]=1[C:16]1(O)[CH:21]2[CH2:22][N:18]([CH2:19][CH2:20]2)[CH2:17]1.O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[F:7][C:16]1([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][N:10]=2)[CH:21]2[CH2:22][N:18]([CH2:19][CH2:20]2)[CH2:17]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 123472(Diethylamino)sulfur trifluorideHCID 197841933-(2-Pyrazinyl)-1-azabicyclo[2.2.1]heptan-3-ol

Product 1

HCID 220975353-Fluoro-3-(2-pyrazinyl)-1-azabicyclo[2.2.1]heptaneYield 14.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethylaminosulphur trifluoride (0.42 g, 2.62 mmol) was added to a stirred solution of 3-(2-pyrazinyl)-1-azabicyclo[2.2.1]heptan-3-ol (0.5 g, 2.62 mmol) in dichloromethane (30 ml), at -65° C. After 24 h, water (20 ml) was added, basified with potassium carbonate, and extracted into dichloromethane (3×50 ml). The combined extracts were dried (Na2SO4), evaporated, and the residue chromatographed through silica-gel, eluting with dichloromethane-methanol (90:10) to give 3-fluoro-3-(2-pyrazinyl)-1-azabicyclo[2.2.1]heptane (75 mg). The compound was further purified as the hydrogen chloride salt, m.p. 245° C. (dec.) (isopropylalcohol); (Found: C, 52.33; H, 5.79; N, 17.97. C10H12F.HCl requires C, 52.29; H, 5.66; N, 18.30%) m/e 193 (M+ for free base); δ(360 MHz, CDCl3) 1.06-1.13 (1H, m, CH of CH2 --N); 1.44-1.55 (1H, m, CH of CH2 --N); 2.58 (1H, dd, J=3.1 and 9.7 Hz, CH of CH2 --N); 2.65-2.72 (1H, m, CH of CH2 --N); 2.83-2.91 (2H, m, CH-bridgehead and CH of CH2 --N); 3.09-3.24 (2H, m, 2 of CH of CH2 --N); 3.59 (1H, ddd, J=3.1, 13.6 and 20.8 Hz, CH of CH2 --N); 8.50-8.53 (2H, m, 2 of pyrazine-H); 8.91 (1H, d, J=1.2 Hz, pyrazine-H).

Workup

  1. extractionextracted into dichloromethane (3×50 ml)
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. customevaporated
  4. customthe residue chromatographed through silica-gel
  5. washeluting with dichloromethane-methanol (90:10)

Sources & evidence

ORD record
ord-e15660f85e754ec29a8530524fb8a381
Source dataset
uspto-grants-1993_11
Patent number
US05260293

Reaction notes

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