Formaldehyde → 4-{5-[(1S,4S)-2-Oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl]-1H-tetrazol-1-yl}-2-(trifluoromethyl)benzonitrile

HRID 517775Notes

Reaction equation

HRID 517775 reaction equation
[CH2:1]=O.[C@H:3]12[CH2:9][C@H:6]([NH:7][CH2:8]1)[CH2:5][O:4]2.C[Si]([N:14]=[N+:15]=[N-:16])(C)C.[N+:17]([C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([C:27]([F:30])([F:29])[F:28])[CH:20]=1)#[C-:18]>CO>[C@H:3]12[CH2:9][C@H:6]([N:7]([CH2:1][C:18]3[N:17]([C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([C:27]([F:28])([F:29])[F:30])[CH:20]=4)[N:16]=[N:15][N:14]=3)[CH2:8]1)[CH2:5][O:4]2

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 78378AzidotrimethylsilaneHCID 11159293(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrobromideHCID 251923904-Isocyano-2-(trifluoromethyl)benzonitrile

Product 1

HCID 666543904-{5-[(1S,4S)-2-Oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl]-1H-tetrazol-1-yl}-2-(trifluoromethyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of formaldehyde (37% in water) (0.076 ml, 1.02 mmol) in methanol (4 ml) was added (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane (101 mg, 1.02 mmol, commercially available for example from InterChim, Montlucon, France). The reaction mixture was stirred at room temperature for 2 hours before the addition of trimethylsilylazide (0.135 ml, 1.02 mmol) and 4-isocyano-2-(trifluoromethyl)benzonitrile (200 mg, 1.020 mmol, commercially available, for example from Priaxon, Munich, Germany). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was partitioned between DCM (50 ml) and water (20 ml). The aqueous layer was extracted with DCM (50 ml). The organic layers were combined, passed through a phase separator and concentrated. The residue was purified by MDAP. Relevant fractions were combined and the solvent removed. The compound was dissolved in 2 ml of DCM and 0.163 ml of 1M HCl in water was added. The solvent was removed to afford the title compound as a white solid (63 mg).

Workup

  1. customThe reaction mixture was partitioned between DCM (50 ml) and water (20 ml)
  2. extractionThe aqueous layer was extracted with DCM (50 ml)
  3. concentrationconcentrated
  4. customThe residue was purified by MDAP
  5. customthe solvent removed
  6. dissolutionThe compound was dissolved in 2 ml of DCM
  7. addition0.163 ml of 1M HCl in water was added
  8. customThe solvent was removed

Sources & evidence

ORD record
ord-b37c79b887234c5a8f39bf934601472c
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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