化合物12的制备To a clean and dry reactor were charged N,N-dimethylformamide (10.32 kg, 141.22 mol; 1.3 equiv) and dichloromethane (DCM) (100.0L). The clear solution was cooled to −10 °C under a nitrogen atmosphere and was added a solution of oxalyl chloride (17.92 kg, 141.22 mol, 1.3 equiv) in DCM (40.0 L) over a period of 60 min. During the addition, a white precipitate was formed. The reaction mixture was allowed to warm up to 25 °C and was stirred for 30 min. The reaction mixture was again cooled to −10 °C. To the reaction mixture was added a solution of 10 (28.30 kg, 282.43 mol, 2.6 equiv) in DCM (40.0 L) by keeping the internal temperature below 5 °C. The reaction mixture was allowed to warm up to 25 °C and was stirred for 30 min under nitrogen. The pale yellow homogeneous solution was cooled again to −10 °C. To the reaction mixture was added a premixed solution of 11 (20.00 kg, 108.63 mol, 1.0 equiv) and triethylamine (31.30 kg, 309.60 mol, 2.85 equiv) [Preparation:To a clean and dry reactor was charged triethylamine (31.30 kg, 309.60 mol, 2.85 equiv) and cooled to 0 °C. 11 (20.0 kg, 108.63 mol, 1.0 equiv) was added dropwise, keeping the internal temperature below 5 °C] by keeping the internal temperature below 0 °C. The yellow heterogeneous reaction mixture was stirred for 5 min, whereupon 1 N aqueous hydrochloric acid (150 L) was added at a temperature below 8 °C. The resultant two-phase mixture was separated, and the aqueous phase was extracted with DCM (60.0 L). The combined organic phases were washed twice with 100.0 L of water. The organic layer was taken in a clean and dry reactor, and the solvent was removed under vacuum at a temperature below 35−40 °C to dryness. To the resultant red residue, n-heptane (100.0 L) was added, and the obtained slurry was stirred for 45 min; the reaction mixture was cooled to −25 °C, filtered, and washed with precooled n-heptane (20.0 L) to afford the title compound 12 as a light orange-colored solid. The obtained wet cake was used directly in the next stage without drying (20.8 kg, 72.2% yield, LOD 2.25%, 99.79 HPLC area %). 参考文献acs.oprd.2c00167
