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

Participants

Reaction Steps

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).

Provenance & Evidence