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a. Synthesis of homobivalent butorphan ligands with spacers branched in α-position
a Reagents and conditions: (i) 2 equiv acid, 4 eq LiN(i-Pr)2, THF/heptane/ethylbenzene, −25°C to 50 °C; (ii) cool to −30 °C, addition of dibromide, warm to 40 °C for 1hr; (iii) 4 eq (COCl)2/CH2Cl2/cat. DMF, concentration in vacuo, then 2 equiv butorphan/CH2Cl2/Et3N, rt 24 h.
