酸胺缩合，可以直接酸和胺，高温脱水，硬生生的完成。对于有些底物，钯黑一样可以完成偶联。 案例信息 Under an N2 atmosphere, the sulfonamide 8 (627 g, 1.63 mol) was charged to a reactor followed by the boronic acid 9 (267.4 g, 1.61 mol). To the mixture was added potassium carbonate (449.9 g, 3.36 mol) followed by MeOH (9.40 L) and DI water (1.88 L), between 15 and 35 °C. Palladium black (5.20 g, 48.8 mmol) was added to the reaction mixture, and the temperature was increased to 63-68 °C for 1.0 h (HPLC <1 area % 9). The reaction mixture was cooled to 50-60 °C, filtered through Hyflo Super-Cel (430 g), and the Hyflo Super-Cel was rinsed with warm (50-60 °C) DI water (2.5 L) to displace desired product. The resulting clarified mixture was heated to 60-65 °C, and acetic acid (627 mL) was added dropwise over 1.0 h. The initial portion of the acid addition caused CO2 evolution (addition controlled) as the residual potassium carbonate/bicarbonate was consumed. As the acid addition proceeded, the product 10 began to crystallize. After the acid addition was complete, the mixture was held for 10 min at 65 °C and was subsequently cooled to 35 °C over 1.25 h.The resulting mixture was cooled to 4 °C over 1.0 h and held for 0.5 h. The batch was filtered, washed with DI water (2 3.1 L) and cold MeOH (2 1.57 L), and dried under vacuum at 55-65 °C to constant weight. The 10 (543.47 g, 88.0% isolated yield, 99 area % and 100% ee by HPLC) was isolated as a crystalline solid.
参考文献Organic Process Research & Development 2005, 9, 621-628
