The reported synthesis of 1,7-Bis(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane(DO2A-t-Bu ester), is carried out in three steps as depicted in Scheme 1. First, two amines of commercially available cyclen are protected in the trans positions with a slow addition of CBZCl at 0 °C and stirring overnight. Second, t-Bu bromoacetate is reacted with CBZ-protected cyclen, 3, at 60 °C in the presence of diisopropylethylamine (DIEA) to produce macrocycle 4 in 20 h. Finally, hydrogenation for 1 d removes the CBZ groups yielding the desired product.
