(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)amine → 2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzonitrile

HRID 2075017Notes

Reaction equation

HRID 2075017 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1Br)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[Cu](C#N)[C:36]#[N:37]>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C:36]#[N:37])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

5

Reactant 2

HCID 58966468(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)amineHCID 178418260HCID 178418260, compound

Product 1

HCID 589664932-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzonitrileYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
170 °C

Procedure

A solution of (3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine (6 g, 10.6 mmol) in DMF (20 mL) at room temperature was deoxygenated by bubbling nitrogen gas through the solution for 10 minutes. Copper cyanide (CuCN) (1.14 g, 12.8 mmol) was added to the reaction mixture and it was heated to 170° C. for 16 hours. The reaction was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed twice with saturated aqueous ammonium chloride solution and then washed with brine. It was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (silica gel, 320 g) (eluted over a gradient 5-25% ethyl acetate and hexane) to give 2.59 g (95%) of the title compound as yellow oil. 1H NMR (400 MHz, CDCl3) δ 4.2 (s, 3H) 4.82 (s, 2H) 4.9 (s, 2H) 7.6 (dd, 1H) 7.7 (s, 2H) 7.8(s, 2H) 7.8 (dd, 1H). MS (ES+) Calc: 508.1, Found: 509.2 (M+1).

Workup

  1. customby bubbling nitrogen gas through the solution for 10 minutes
  2. temperatureThe reaction was cooled to room temperature
  3. washThe organic layer was washed twice with saturated aqueous ammonium chloride solution
  4. washwashed with brine
  5. dry with materialIt was dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (silica gel, 320 g) (
  8. washeluted over a gradient 5-25% ethyl acetate and hexane)

Sources & evidence

ORD record
ord-272d45275fc6426b899bf8356519ad16
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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