反应详情

To a solution of 4-amino-2-(2,4-dichlorophenylamino)-3-fluoro-5-isopropenyl-benzoic acid methyl ester (89.9 mg, 0.243 mmol) in THF (2 mL) and conc. H2SO4 (0.050 mL, 0.94 mmol) was added a solution of NaNO2 (24.0 mg, 0.348 mmol) in water (0.5 mL) at 0° C. The reaction temperature was kept below 5° C. during the addition. The reaction mixture was warmed to room temperature, and 2 mL of water was added. After stirring in the dark for 4 days, the reaction mixture was diluted with EtOAc, and washed with water. The organic layer was separated, dried over MgSO4, filtered, and concentrated in vacuo to give the crude material which was purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2) to afford the desired product (54 mg, 58%).

1. additionThe reaction temperature was kept below 5° C. during the addition
2. washwashed with water
3. customThe organic layer was separated
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto give the crude material which
8. customwas purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2)