反应详情

温度

40 °C

To a solution of methyl 3-(chloromethyl)-1-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (3 mL, 0.197M in CH2Cl2, 0.591 mmol) [prepared as described in step 2 of example 40] in anhydrous DMF (5 mL) was added methoxyethanol (0.25 g, 3.29 mmol, 0.26 mL, 5.5 eq.) followed by i-Pr2NEt (0.407 g, 3.14 mmol, 0.55 mL, 4 eq.). The mixture, under nitrogen, was placed in an oil bath and the bath was warmed to 40° C. After stirring for 24 hours (40° C.) the reaction was judged to by complete by HPLC-MS analysis and the volatiles were removed in vacuo (ca. 2 torr) to give a golden yellow oil. The crude material was purified by chromatography on a column of silica gel (40 mm OD, 100 g, 230-400 mesh, packed with CH2Cl2, eluted with CH2Cl2-EtOAc 70:30 v/v, 1.0 L, and CH2Cl2-EtOAc-MeOH 68:30:2, 1.0 L, 25 mL fractions) using the flash technique. Fractions 55-64 were combined to afford 0.148 g (77%) of methyl 1-(2,4-difluorobenzyl)-3-[(2-methoxyethoxy)methyl]-1H-pyrrolo[2,3-c]pyridine-5-carboxylate as a white, crystalline solid.

1. customThe mixture, under nitrogen, was placed in an oil bath
2. customthe volatiles were removed in vacuo (ca. 2 torr)
3. customto give a golden yellow oil
4. customThe crude material was purified by chromatography on a column of silica gel (40 mm OD, 100 g, 230-400 mesh, packed with CH2Cl2, eluted with CH2Cl2-EtOAc 70:30 v/v, 1.0 L, and CH2Cl2-EtOAc-MeOH 68:30:2, 1.0 L, 25 mL fractions)