P,P-Diphenylphosphinic azide → 1-Azabicyclo[3.2.1]oct-5-ylmethyl (5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride

Participants

Reaction Steps

To a solution of 5-phenyl-1,3-thiazole-4-carboxylic acid (400 mg) in toluene (5 mL) was added TEA (380 μL) at room temperature. To the reaction liquid was added dropwise a solution of DPPA (546 μL) in toluene (5 mL), followed by stirring at the same temperature for 20 minutes. After stirring at 90° C. for 5 minutes, a mixture of 1-azabicyclo [3.2.1]oct-5-yl methanol (357 mg) and DMF (2 mL) was added thereto, followed by heating under reflux for 1 hour. To the reaction liquid was added water, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (YAMAZEN YFLC WPrep2XY, CHCl3:MeOH:28% aqueous ammonia=80:10:1) to obtain an oily substance. This was dissolved in EtOAc, followed by addition of 4 M HCl/dioxane at room temperature. The solid precipitated was collected by filtration and washed with EtOAc to obtain 1-azabicyclo[3.2.1]oct-5-ylmethyl (5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride (174 mg) as a white solid.

Provenance & Evidence