列举一步酯交换反应操作制备化合物11To a 2500 L enameled reactor equipped with a NaOH scrubber were charged a solution of 5 in isopropanol from the previous step (666.6 kg of solution, 32% w/w, l.0 equiv based on HPLC assay) and isopropanol (860 L, 3.6 vol). Sulfuric acid (159.3 kg, 2.4 equiv, 86 wt % solution) was added over 15 min, and the mixture was heated to 80−84 °C for 15 h. Isopropanol was distilled at 85 °C and atmospheric pressure over 9 h and replaced with fresh isopropanol (800 L, 3.4 vol). After conversion to the isopropyl ester, the mixture was concentrated by distillation at atmospheric pressure over 9.5 h until the total volume reached640 L.参考文献https://dx.doi.org/10.1021/acs.oprd.9b00427Org. Process Res. Dev. 2020, 24, 1164−1174
