内酰胺片段25的合成
https://doi.org/10.1021/acs.oprd.2c00375
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第一步
需要-78度，为了保证光学选择性，典型数据dr大于99
Hanessian group的实验结论：LiHMDS拔氢烯醇化的低温和淬灭过程的低温对光学选择性影响很大
本文献提示：溴乙腈的预冷和液面下加入，对于光学选择性也是很关键的。
第二步
To a 8000 L glass-lined reactor was charged MeOH (1991kg) and cobalt(II) chloride hexahydrate (275 kg) at 20 °C. The solution was cooled to −5 °C. A solution of 23 in MeOH (1574 kg, (360 kg assay corrected) was charged while keeping the temperature in the range of −15 to 0 °C. Sodium borohydride (173 kg) was added to the reaction mixture in portions. After charging about 50% of the sodium borohydride, it was held for 1−3 h, monitored progress (confirming NMT 50% 23 remaining), and resumed charge. The reaction mixture was held at −10 °C for about 6−10 h and monitored for progress until NMT 2% of 23 remained (charged more sodium borohydride (25 kg portion) to reach completion as needed). Upon meeting reaction completion criteria, the reaction mixture was warmed to 10−15 °C and held for at least 12 h. The reaction mixture was sampled every 4−6 h until conversion to 3 from 24 indicated NMT 2% of 24 remained.
