实验操作General Procedure for the N-Methylation of Pyrroles with DMC/DMF/DABCO. (Example: Methyl-N-methyl-2-pyrrole Carboxylate (7)). A reaction flask was charged with methyl-2-pyrrole carboxylate, 5 (2.0 g, 16.0 mmol), DMC (20mL), DABCO (0.18 g, 1.6 mmol), and DMF (1.0 mL). The resulting mixture was heated to 90-92 °C and stirred at that temperature for 23 h. HPLC analysis indicated complete consumption of the starting material. The reaction mixture was cooled to 21 °C, diluted with EtOAc (25 mL), and transferred to a separatory funnel. The solution was washed sequentially with H2O (25 mL) and 10% citric acid (2 × 15 mL). The washes were combined and back extracted with EtOAc (25 mL). The combined organics were washed with brine (25 mL), dried over Na2SO4, and concentrated in Vacuo to afford the desired product as a colorless oil (2.0 g, 90.4%). 参考文献Organic Process Research & Development 2009, 13, 1199–1201
案例二
反应过程
放大实验操作Dimethyl carbonate (128.4 kg, 1.427 ×103 mol), 3,5-dimethoxybenzoic acid (130 kg, 0.714 × 103 mol)and conc. H2SO4 (14.3 kg, 0.14 × 103 mol) were charged into a 630 L GLR, and the mixture was heated to 85-90 °C with steam under stirring. The temperature was maintained for 6 h. TLC showed not more than 1% of the starting acid. The reaction mass was cooled to 25-30 °C, DM water (390 L) was added, and the mixture was stirred for 1 h at 10-15 °C. The solid obtained was centrifuged and washed with DM water (260 L). The solid was dried under vacuum at 25-30 °C until moisture content by Karl Fischer was less than 3%. The yield of methyl 3,5-dimethoxy benzoate was 138 kg (98.5%, purity: 99.54%), mp 35-39 °C (rep 31-33 °C) with a moisture content of 2.9%. 参考文献Organic Process Research & Development 2009, 13, 769–773
