反应详情

Step H (1): (R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate. To a solution of 3-bromo-5-(methoxycarbonyl)benzoic acid (1.8 g, 6.95 mmol) in dichloromethane (100 mL) and was added Hunig's base (2.7 g, 20.85 mmol) to make a clear solution and HATU (3.17 g, 8.34 mmol) was then added. After stirring for 30 min, the reaction mixture was added (R)-2-(methoxymethyl)pyrrolidine (800 mg, 6.95 mmol) and the reaction mixture was stirred at rt for 6 h. Dichloromethane (100 mL) was added and the mixture was washed with 1N NaOH, H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient) to give 1.8 g of the title compound (73% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 1.77-2.08 (4H, m), 3.14-3.47 (5H, m), 3.63 (2H, brd s), 3.82 (3H, s), 4.41 (1H, brd s), 7.83 (1H, s), 8.07 (1H, s), 8.20 (1H, m).

1. additionwas then added
2. stirringthe reaction mixture was stirred at rt for 6 h
3. washthe mixture was washed with 1N NaOH, H2O
4. concentrationconcentrated under vacuum
5. customThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient)