Ethyl chloroformate → N-(1-(4-((4-(4-fluorophenyl)piperazin-1-yl)methyl)phenyl)cyclopropyl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a suspension of 1-(4-((4-(4-fluorophenyl)piperazin-1-yl)methyl)phenyl)cyclopropanecarboxylic acid (1.73 g) in water (1.7 ml) was added acetone (7 ml) and dissolved therein. A solution of triethylamine (0.75 ml) in acetone (10 ml) was added under ice-cooling and a solution of ethyl chlorocarbonate (0.56 ml) in acetone (4 ml) was added dropwise over 15 min. The mixture was stirred at 0° C. for 30 min. To this solution was added dropwise a solution of sodium azide (0.48 g) in water (3 ml) under ice-cooling over 10 min. The mixture was stirred for 30 min. The reaction mixture was poured into ice water (100 ml) and extracted with diethyl ether. The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated to give an oil. The oil was dissolved in toluene (17 ml) and heated at 100° C. for 1 hr. The reaction mixture was ice-cooled and methylmagnesium iodide (1M, diethyl ether solution) (4.3 ml) was added. The mixture was stirred at room temperature for 30 min. The reaction mixture was poured into aqueous ammonium chloride and extracted with water and ethyl acetate (100 ml). The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (developing solvent; ethyl acetate:methanol=100:1) and recrystallized from ethyl acetate-isopropyl ether to give the title compound (0.52 g) as white crystals.

Provenance & Evidence