Ullmann Coupling to acid 3. The Ullmann reaction between acid 1 and aminopyridine 2 to form 3 was performed in an aqueous solution of 2 wt % TPGS-750-M 14 at a global concentration of 1 M. Purification involved acidification of the aqueous medium to pH 4.0, followed by collection of the precipitated product 3 via filtration. Copper salts were most efficiently removed by centrifugation rather than by suction filtration as the latter approach created a large amount of foam. Unreacted aryl acid 1 could be isolated by further acidification of the filtrate to pH 1, collection by filtration, and recrystallization from EtOH and water. Optimization involving the amount of catalytic copper, and the role of the surfactant were screened (Table ). Increasing the loading of CuI from 5 mol % to 10 mol % led to a moderate increase in yield (entry 2). The importance of the surfactant was also apparent, as in its absence, the yield was reduced accordingly (entries 3 and 4), thus the conditions in entry 2 were selected. Some surfactant remained in the precipitated product, although the yields in entries 1 and 2 do not reflect this. Importantly, the product could be used without further purification and the residual surfactant did not impact the yield or purity of the subsequent cyclization/deoxychlorination step (87% overall yield for both steps, vide infra). It is noteworthy that product 3 was obtained with very high regioselectivity (i.e., no substitution at the paraposition was observed by HPLC). Cyclization/deoxychlorination to aryl chloride 4. Cyclization and concomitant deoxychlorination of compound 3 to form heteroaromatic 4 was achieved using POCl3 (Scheme 2). Et3N was included to prevent evolved HCl from demethylating the methoxy group and leading to impurity I (Figure ) following subsequent deoxychlorination. Although water could not be used in this step due to the water-sensitive nature of POCl3, toluene served nicely and could be recovered following isolation of product 4, thereby limiting organic waste generation. The product was obtained in 87% yield.