反应详情

温度

122.5 °C

To a mixture of 5,6,7,8-tetrahydroquinazoline-2,4(1H, 3H)-dione (10.4 g, 62 mmol) and hexamethyldisilazane (HMDS, 33 mL, 158 mmol) in toluene (100 mL) was added concentrated sulfuric acid (0.34 mL, 6.2 mmol) at r.t. The mixture was heated to reflux overnight until a clear solution was obtained. After the removal of toluene and excess HMDS with vacuum evaporation, methyl 3-bromomethylbenzoate (16 g, 70 mmol) was added to the residue. The reaction mixture was heated to 115-130° C. and was stirred at this temperature for 4 h. The reaction mixture was diluted with 1,4-dioxane (6 mL) and methanol (100 mL) at 100° C., and was stirred for 30 min. The reaction mixture was evaporated to remove the solvent. The residue was dissolved in ethyl acetate (EA, 300 mL) and washed by 1N hydrochloric acid (100 mL×1) and water (100 mL×3). The organic layer was dried with anhydrous sodium sulfate and evaporated to give the crude product, which was purified by column chromatography on silica gel (petroleum ether: ethyl acetate=2:1) to give the title compound (2.3 g, 12% yield) as yellow powder. 1H NMR (DMSO-d6): 11.40 (s, 1H), 7.87 (d, J=7.5 Hz, 1 H), 7.79 (s, 1H), 7.55-7.44 (m, 2H), 5.12 (s, 2H), 3.85 (s, 3H), 2.45-2.35 (m, 2H ), 2.25-2.20 (m, 2H), 1.65-1.40 (m, 4H). MS: m/z 315.4 [M+H]+.

1. temperatureThe mixture was heated
2. temperatureto reflux overnight until a clear solution
3. customwas obtained
4. customAfter the removal of toluene and excess HMDS
5. additionwas added to the residue
6. stirringwas stirred for 30 min
7. customThe reaction mixture was evaporated
8. customto remove the solvent
9. dissolutionThe residue was dissolved in ethyl acetate (EA, 300 mL)
10. washwashed by 1N hydrochloric acid (100 mL×1) and water (100 mL×3)
11. dry with materialThe organic layer was dried with anhydrous sodium sulfate
12. customevaporated
13. customto give the crude product, which
14. customwas purified by column chromatography on silica gel (petroleum ether: ethyl acetate=2:1)