1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-[(1S)(4S)-2-benzyl-2,5-diazabicyclo{2,2,1}heptan-5-yl]-3-fluoro-1-nitrobenzene

HRID 1167501Notes

Reaction equation

HRID 1167501 reaction equation
Br.Br.[CH2:3]([N:10]1[CH2:15][C@@H:14]2[CH2:16][C@H:11]1[CH2:12][NH:13]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:17][C:18]1[CH:19]=[C:20]([N+:25]([O-:27])=[O:26])[CH:21]=[CH:22][C:23]=1F.N12CCCN=C1CCCCC2>C(#N)C>[CH2:3]([N:10]1[CH2:15][C@@H:14]2[CH2:16][C@H:11]1[CH2:12][N:13]2[C:23]1[CH:22]=[CH:21][C:20]([N+:25]([O-:27])=[O:26])=[CH:19][C:18]=1[F:17])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 14612542(1S,4S)-2-Benzyl-2,5-diazabicyclo(2.2.1)heptane--hydrogen bromide (1/2)

Product 1

HCID 213566044-[(1S)(4S)-2-benzyl-2,5-diazabicyclo{2,2,1}heptan-5-yl]-3-fluoro-1-nitrobenzeneYield 97%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (1S)(4S)-2-benzyl-2,5-diazabicyclo{2,2,1}heptane dihydrobromide [Henry et al. J. Med. Chem. (1974), 17, 481] (1.05 g, 3 mmol), 3,4-difluoronitrobenzene (0.48 g, 3 mmol) and 1,8-diazabicyclo[5,4,0]undec-7-ene (1.38 g, 9 mmol) in acetonitrile (10 ml) was stirred and heated at reflux for 2 hours. Solvent was evaporated and the residue was partitioned between EtOAc and water. The organic layer was filtered (1PS paper) and the filtrate evaporated to give 4-[(1S)(4S)-2-benzyl-2,5-diazabicyclo{2,2,1}heptan-5-yl]-3-fluoro-1-nitrobenzene (0.95 g, 97%) as a solid. MS: 328 (M+); NMR(CDCl3); 1.82-2.07 (2H, dd); 2.77-2.98 (2H, dd); 3.59 (2H+1H, s); 3.72 (2H, s); 3.91 (1H, m); 4.58 (1H, s); 6.6 (1H, t); 7.2-7.34 (5H+CHCl3);

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 hours
  3. customSolvent was evaporated
  4. customthe residue was partitioned between EtOAc and water
  5. filtrationThe organic layer was filtered (1PS paper)
  6. customthe filtrate evaporated

Sources & evidence

ORD record
ord-877a492c494a43f8bebd3015d3a6dcf7
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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