To maintain the production schedule and due to tight timeline, this addition method was abandoned, and a two-reactor system was deployed thus avoiding formation of undesired 17A in its entirety. This method was reproduced multiple times on various scales with no decrease in performance. (Entries 6 to 8). Ultimately, compound 16 was treated with iPrMgCl.LiCl in THF in the presence of catalytic amount of CuI. The in-situ generated organomagnesium species was then slowly added to acetic anhydride. After work-up, the desired tert-butyl 5-acetyl-2morpholinoisonicotinate 17 was isolated in 77% corrected yield (average of several runs). a Reactions were run at the indicated scale of tert-butyl 5-bromo-2-morpholinoisonicotinate 16 in THF (5V). b Determined by HPLC. c Inverse = Metalated species added to Ac2O at -50 °C. d Normal = Ac2O added to the metalated species at -50 °C. e Normal-slow = very slow addition (1-2 L.h -1 ) of Ac2O to the metalated species at -50 °C.