Example 15
PLA (D/L-polylactide) (Resomer R202H from Boehringer-Ingelheim, KOH equivalent acid number of 0.21 mmol/g, intrinsic viscosity (iv): 0.21 dl/g) (10 g, 2.1 mmol, 1.0 eq) was dissolved in dichloromethane (DCM) (35 mL). EDC (2.0 g, 10.5 mmol, 5 eq) and NHS (1.2 g, 10.5 mmol, 5 eq) were added. The solids were dissolved with the aid of sonication. The resulting solution was stirred at room temperature for 6 days. The solution was concentrated to remove most of DCM and the residue was added to a solution of 250 mL of diethyl ether and 5 mL of MeOH to precipitate out the activated PLA-NHS ester. The solvents were removed and the polymer was washed twice with ether (2×200 mL) and dried under vacuum to give PLA-NHS activated ester as a white foamy solid (˜8 g recovered, 1H NMR confirmed the presence of NHS ester). The PLA-NHS ester is stored under argon in a below −10° C. freezer before use.
Alternatively, the reaction can be performed in DMF, THF, dioxane, or CHCl3 instead of DCM. DCC can be used instead of EDC (resulting DCC-urea is filtered off before precipitation of the PLA-NHS ester from ether). The amount of EDC or DCC and NHS can be in the range of 2-10 eq of the PLA.