4,7-Diaza-spiro[2.5]octane-7-carboxylic acid tert-butyl ester

Starting from diethyl malonate (1), 1,1-cyclopropanedicarboxylate (2) was prepared by cyclization reaction; 2 was hydrolyzed to obtain 1,1-cyclopropanedicarboxylate monoethyl ester (3); 3 was rearranged by Hoffmann reaction to obtain ethyl 1-tert-butoxycarbonylamino-1-cyclopropanecarboxylate (4); 4 was hydrolyzed to obtain 1-tert-butoxycarbonylamino-1-cyclopropanecarboxylic acid (5); 5 was acylated by ethyl α-aminoacetate to obtain Ethyl 1-tert-butoxycarbonylamino-1-cyclopropanecarbonylaminoacetate (6); 6 was cyclized again with ethylene glycol to give 5,8-diketone-4,7-diazaspiro[2.5]octane (7); 7 was reduced to give 4,7-diazaspiro[2.5]octane (8); 8 was added to di-tert-butyl dicarbonate to synthesize 4,7-diazaspiro[2.5]octane-7-carboxylic acid tert-butyl ester, with an overall yield of 9.16%.