Mix propane-2-sulfonic acid {2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl) -phenyl]-thiophen-3-yl}-amide (1.00 equiv; 441.02 mmoles; 196.60 g), 3-ethoxy-4-iodo -benzoic acid ethyl ester (1.00 equiv; 441.47 mmoles; 141.27 g), DME (15.15 moles; 1.57 L; 1.37 kg), PdCl2(dppf) (2.42 mmoles; 1.97 g), and ethanol (13.57 moles; 790.00 mL; 625.13 g) under a N2 atmosphere. Then add Na2CO3 2M in water (1.89 equiv; 833.06 mmoles; 416.53 mL; 504.00 g) and heat the reaction mixture to reflux until HPLC monitoring indicates reaction completion. Cool reaction mixture to RT then add water (109.13 moles; 1.97 L). Separate the organic layer, filter through diatomaceous earth, then concentrate organic layer under reduced pressure. Add ethanol (2.36 L), and remove solvent under reduced pressure. Add 3-Mercaptopropyl-functionalized Silica Gel (50.00 g), and heat to 60° C. for 30 minutes. Cool to RT then filter over diatomaceous earth. Rinse cake with ethanol, then combine ethanol washes and filtrate. Add 14% Sodium Hydroxide (4.89 moles; 1.27 L; 1.43 kg) and heat the reaction mixture at 55° C. until monitoring by HPLC indicates the end of the reaction. Cool to RT then add 7N HCl to the reaction mixture. Stir the resulting precipitate overnight. Filter the reaction mixture and wash cake with EtOH/Water (40/60-v/v) (180.78 g), EtOH (155.49 g), and n-heptane (262 g). Redissolve cake in acetone (2.18 kg) and add activated charcoal (46 g). Heat the reaction mixture at 50° C. for 30 minutes. Cool to RT, filter over diatomaceous earth (765.59 mmoles; 200.00 g), and concentrate under reduced pressure. Cool to RT, then add n-Heptane (7.73 moles; 1.13 L; 775. 00 g) and stir for 1 h. Fltere and wash cake with n-heptane/acetone 60/40 (2.58 moles; 354.79 mL) and dry under reduced pressure to yield 124 g of the title compound.
