Background and overview of the preparation method of benzyl-1-piperazine carbonate
Benzyl-1-piperazine carbonate is an organic intermediate that can be made from six Hydrated piperazine is used as raw material to first prepare piperazine-1-carboxylic acid tert-butyl ester, then react with CbzCl to obtain piperazine-1-carboxylic acid tert-butyl ester-4-carboxylic acid benzyl ester, and finally remove Boc protection to obtain benzyl- 1-Piperazine carbonate.
Preparation method of benzyl-1-piperazine carbonate
Place 30.16 grams (0.1536 mol) of piperazine hexahydrate, 150 ml of water and 185 ml of tert-butyl alcohol in an ice bath. When cooled to 5°C, add 24.4 ml of 2.5N sodium hydroxide dropwise, and then slowly add 13.5 g ( 0.061 mol) di-tert-butoxycarboxylic anhydride, and stir for one hour at 5-6°C, stir at room temperature overnight, evaporate tert-butyl alcohol under reduced pressure, filter to remove the double-protected solid (melting point 162-163°C), and use dichloride to filter the filtrate. Extract three times with methane, wash with water, wash with salt, dry over anhydrous magnesium sulfate, filter through anhydrous sodium sulfate, concentrate under reduced pressure, cool and crystallize in ice water and filter to obtain the white solid product piperazine-1-carboxylic acid tert-butyl ester (melting point 47- 49℃).
Dissolve 10 g (54 mmol) piperazine-1-carboxylic acid tert-butyl ester and 8.2 ml triethylamine in 120 ml methylene chloride, cool to 0°C, and add 9.2 g ( 54 mmol) benzyloxyformyl chloride and 100 ml of methylene chloride, stir at room temperature until the raw materials disappear, concentrate under reduced pressure, add ethyl acetate, wash with water, sodium bicarbonate, salt, dry over anhydrous sodium sulfate, and spin off Solvent, short column separation of heavy calcium carbonate to obtain the product piperazine-1-carboxylic acid tert-butyl ester-4-carboxylic acid benzyl ester.
Dissolve 4.14 g (12.9 mmol) of piperazine-1-carboxydimethylsulfoxide tert-butyl ester-4-carboxylic acid benzyl ester in 30 ml of methylene chloride, cool to 0℃ , add 10 ml of trifluoroacetic acid, stir at room temperature until the raw material disappears, concentrate under reduced pressure, add 150 ml of 1N sodium hydroxide to neutralize, extract twice with dichloromethane, dry over anhydrous magnesium sulfate, spin off the solvent to obtain the product benzyl- 1-Piperazine carbonate.
References
[1] [Invented in China, authorized by China] CN200810008196.3 Pyrimidine thiazolamide derivatives, their preparation methods, pharmaceutical compositions and uses
