The poor aqueous solubility of many drugs can be overcome by formulation as amorphous solid dispersions (ASD) in cellulosic-based polymer matrices. Cellulose esters containing adipates and other ester groups have shown great promise as new ASD polymers. Previous attempts to synthesize these cellulose adipate esters by direct reaction of cellulose derivatives with adipic anhydride failed due to crosslinking and gelation, caused by formation of poly(adipic anhydride) and subsequent reaction of the poly(anhydride) with cellulosic hydroxyls. In order to develop direct, efficient syntheses of these pH-sensitive cellulose adipate derivatives, we have developed new synthetic procedures that cleanly afford soluble ester products by direct condensation with adipic anhydride, that show no evidence of crosslinking. A series of cellulose ester adipates has been synthesized by this direct route, containing substantial adipate DS (up to 0.53). This new method requires no complex solvents or protective groups, and is an effective and versatile route to these useful materials. Reaction of cellulose acetate propionate (CAP-504-0.2) with adipic anhydride