Boc-3-azabicyclo[3.1.0]hexane-2-carboxylic acid synthesis

Yield:-

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in dichloromethane for 22 h;

Steps:

A.8.1
A.8 Synthesis of 2-aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester A.8.1 Synthesis of 3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-tert-butyl ester; DIPEA (249 mmol, 1.1 Oeq) and a solution of di-tert-buty dicarbonate (238 mmol, 1.05eq) in DCM (100 mL) are added successively to a suspension of 3-aza- bicyclo[3.1.0]hexane-2-carboxylic acid (226 mmol, l.Oeq) in DCM (400 mL). The mixture is stirred for 22h and concentrated in vacuo to a volume of approximately 100 mL. EtOAc (200 mL) is added and the mixture is made acidic (pH 3) by addition of aq. citric acid solution. The layers are separated and the aq. layer is extracted three times with EtOAc (100 mL each). The combined organic layers are washed with brine, dried over MgSO₄ and concentrated in vacuo to give the desired carboxylic acid as an viscous oil which is used without further purification. LC-MS: t_R = 0.75 min; [M+H]⁺ = 228.1.

References:

ACTELION PHARMACEUTICALS LTD WO2008/38251, 2008, A2 Location in patent:Page/Page column 94-95