部分实验操作Compound 24. 289.8 kg of ethyl trifluoroacetate (1.2 equiv) was charged to the 13 (164.9 kg) in MTBE solution prepared above. Then, 248 kg of KOt Bu (1.3 equiv) in 702 kg of 2-MeTHF solution was transferred to the substrate solution over 1.5 h at 3 to 13 °C. The contents were adjusted from 11 to 20 °C and the reaction mixture was agitated at 20 to 22 °C. The reaction was completed within 3.0 h. The reaction mixture as a slurry was used as is in the step 6 below. Compound 22. The 24 slurry prepared above was transferred to an 11,000 L glass-lined reactor, and the slurry was adjusted to 8 °C. A 950.1 kg portion of prepared phosphoric acid solution was transferred to the substrate slurry over 2 h at 7 to 11 °C. Using a hopper, 129.0 kg of sodium nitrite was charged in 14 portions at 22 to 27 °C. The reaction mixture was agitated at 24 to 28 °C and the reaction was completed within 4 h. After the reaction was completed, 10 V of purified water was charged to the reaction mixture. The resulting mixture was agitated for 0.5 h at 25 °C and settled for 0.5 h. After phase separation, the bottom aqueous layer was transferred to a 12,000 L glass-lined reactor and extracted with 8 V of 2-MeTHF. The lower aqueous layer was transferred to a 10,000 L glass-lined reactor and extracted with 2-MeTHF (8 L/kg). The lower aqueous layer was transferred and extracted with 5 V of 2-MeTHF. The first organic layer was transferred to a 10,000 L glass-lined reactor and concentrated during the back extraction. Each organic layer from back extraction was transferred to this reactor, and the solution continued to be concentrated. The concentration required 11.5 h with TJ = 50 °C and the final content volume was adjusted to 5 L/kg after concentration. The concentrate was transferred to a 4000 L glass-lined reactor and continued to concentrate to 3 L/kg for 2 h with TJ = 50 °C. A 4.0 V portion of 2-MeTHF was charged, and the contents were concentrated to 2.5 L/kg for 2.5 h with TJ = 50 °C. The purity of the resulting 22 solution was 97.5% by HPLC 参考文献https://doi.org/10.1021/acs.oprd.4c00235
