3-Azabicyclo[3.1.0]hexane-3-carboxylicacid,6-amino-,1,1-dimethylethylester,

(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexane-3-carboxylic Acid 1,1-Dimethylethyl Ester, is an intermediate in the preparation of a novel series of Histone Deacetylase (HDAC) Inhibitors, demonstrating class I selectivity and good oral bioavailability. It can also be used in the synthesis of Alatrofloxacin Mesylate (A511400).

Tert-butyl REL-(1R,5S,6S)-6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate was prepared by using tert-butyl chloroformate and 3-azabicyclo[3.1.0]hexan-6-amine as starting materials.

Take a dry three-necked reaction flask, one fitted with a calcium chloride desiccator, one fitted with a dropping funnel, and the tetrahydrofuran solution needs to be anhydrous in advance. Weigh the tert-butyl ester formyl chloride dissolved in 180mL of anhydrous tetrahydrofuran solution, start the stirring device. After dissolution, the solution was slowly added to 200 mL of tetrahydrofuran solution under ice-water bath conditions (3-azabicyclo[3.1.0]hexan-6-amine had been dissolved in tetrahydrofuran solution), and a solid precipitated immediately, and the stirring was continued for 4 hr at 35 after the addition, and the progress of the reaction was detected by thin-layer chromatography. When the reaction was completed and the reaction solution was cooled, 400 mL of ice water was added to the reaction to make the product precipitate completely, and a light yellow solid was obtained by filtration. After drying and crystallization with anhydrous ethanol, tert-butyl REL-(1R,5S,6S)-6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate was obtained.