Acetic Acid → HCID 86691888, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of dimethyl(2-{1-[4-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}ethenyl)amine (may be prepared as described in Intermediate 4) (100 mg, 0.353 mmol) in ethanol (2 mL) was added (cis)-2,6-dimethylmorpholine (122 mg, 1.059 mmol, Alfa Aesar, Ward Hill, USA) and acetic acid (0.061 mL, 1.059 mmol). The reaction mixture was heated to 65° C. and stirred for 4 hours. The reaction mixture was cooled and the solvent removed under vacuum. The residue was dissolved in ethanol (2 mL) before the addition of further (cis)-2,6-dimethylmorpholine (122 mg, 1.059 mmol) and acetic acid (0.061 mL, 1.059 mmol). The reaction mixture was heated to 65° C. and stirred for 3 hours. The reaction mixture was cooled and the solvent removed under vacuum. The solid residue was partitioned between DCM (3 mL) and saturated aqueous NaHCO3 (2 mL). The organic layer was collected via a hydrophobic frit and the solvent removed under vacuum. The residue was dissolved in dry dichloromethane (DCM) (2 mL) before the addition of sodium triacetoxyborohydride (224 mg, 1.06 mmol). The reaction mixture was shaken at room temperature for 18 hours. The reaction mixture was partitioned between DCM (3 mL) and saturated aqueous NaHCO3 (2 mL). The organic layer was collected via a hydrophobic frit and the solvent removed under vacuum. The residue was purified by MDAP. Fractions containing the desired product were combined and the solvent removed. The residue was dissolved in methanol and passed through a 1 g SAX cartridge, eluting once with methanol. The methanol fractions were combined and the solvent removed to yield a yellow gum. The gum was dissolved in a minimum of methanol and 1N HCl in diethyl ether (2 mL) added. The solvent was removed under a stream of argon to yield a sticky orange gum. The product was partitioned between saturated aqueous NaHCO3 (1 mL) and DCM (1 mL). The organic layer was collected via a hydrophobic frit and the solvent removed under vacuum. The product was further purified by silica chromatography (Biotage SP4 eluting a gradient from 50-100% EtOAc over 15 column volumes) to yield the title compound as a solid (12 mg).

Provenance & Evidence