Sandmeyer Reaction：引入氯代物的工藝案例

  • 2024-06-27 06:59
  • 原料藥合成工藝開發
案例
  • 化合物25的製備

實驗操作
2-amino-3- cyano-5-ethylpyrazine 1-oxide 24 (29.6 kg, 153 mol corrected by QNMR, 1.00 equiv) and sodium nitrite (24.2 kg, 352 mol, 2.30 equiv) were added portion-wise into the mixture of concentrated hydrochloric acid (125 kg) and water (500 L) at 0−10 °C. After stirring for 30 min at 0−10 °C。

DCM (125 L) was added, and the aqueous layer was separated after stirring for 10 min. Then, the aqueous layer was washed with DCM (125 L) 3 times, and all organic layers were combined and washed with water (50.0 L). The organic layer was kept in the reactor until the other eight batches were produced (total input of 2-amino-3-cyano-5-ethylpyrazine 1-oxide 24 was 253 kg [1300 mol corrected by QNMR]). The organic layers from all nine batches were concentrated to 350 L. Toluene (739 L) was added, and then concentrated to 750 L that contained 2- chloro-3-cyano-5-ethylpyrazine 1-oxide 25 (173 kg, 941 mol, 72.4%, 89.9 A% by HPLC method A). A small amount of the solution was concentrated to afford an off-white solid

參考文獻
https://doi.org/10.1021/acs.oprd.4c00119