30.16 g (0.1536 mol) of piperazine hexahydrate was placed in an ice bath with 150 mL of water and 185 mL of tert-butanol.
in an ice bath, cooled to 5 C. 24.4 mL of 2.5 N sodium hydroxide was added dropwise, followed by the slow dropwise addition of 13.5 g (0.061 mol) of
Di-tert-butoxyformic anhydride and kept stirring at 5-6C for one hour, stirred overnight at room temperature, evaporated off the tert-butanol under reduced pressure, over
filtration to remove the biprotected solid (melting point 162-163C), the filtrate was extracted three times with dichloromethane, washed with water, washed with salt, anhydrous
Magnesium sulfate was dried, filtered through anhydrous sodium sulfate, concentrated under reduced pressure, and filtered by cooling the crystallization in ice water to give the white solid product tert-butyl piperazine-1-carboxylate (solubility point 47-49C).
Ten grams (54 mmol) of tert-butyl piperazine-1-carboxylate and 8.2 mL of triethylamine were dissolved in 120 mL of di-
chloromethane, cooled to 0C, 9.2 g (54 mmol) of benzyloxycarbonyl chloride and 100 mL of dichloromethane were added dropwise to the
solution, stirred at room temperature until the raw material disappeared, concentrated under reduced pressure, added ethyl acetate, washed with water, washed with sodium bicarbonate, washed with salt, dried over anhydrous sodium sulfate, spun off the solvent, and separated on a short column to obtain the product piperazine-1-carboxylic acid tert-butyl ester-4-carboxylic acid benzyl ester.
Dissolve 4.14 g (12.9 mmol) of tert-butyl piperazine-1-carboxylate-4-carboxylic acid benzyl ester in 30 ml of dichloromethane, cool to 0C, add 10 ml of trifluoroacetic acid, stir at room temperature until the raw material disappeared, concentrate under reduced pressure. Add 1N sodium hydroxide 150 ml neutralization, extracted twice with dichloromethane, anhydrous magnesium sulfate dry, spin off the solvent to get the product benzyl-1-piperazine carbonate.
