Sulfuric Acid → 1h-Benzimidazole-2-propanoic acid, ethyl ester

Temperature

80 °C

To a stirred solution of benzene-1,2-diamine (20.0 g, 0.19 mol, 1.0 eq.) in dioxane (500 mL) at room temperature, was added succinic anhydride (22.2 g, 0.22 mol, 1.2 eq.), and the reaction mixture was heated to 80° C. and stirred at that temperature for 16 hours. The resulting precipitate was filtered and washed with dioxane (100 mL), water (100 mL) and diethyl ether (100 mL) to give a white solid. The solid was suspended in ethanol (400 mL), and concentrated sulfuric acid (10 mL) was added at room temperature. The reaction mixture was heated to reflux and stirred at that temperature for 20 hours. The reaction was then cooled to room temperature and concentrated in vacuo. Water (100 mL) was added, and the mixture was adjusted to pH 7 with 1 M aqueous NaOH solution. The aqueous layer was extracted into ethyl acetate (3×100 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo to give 6a as a pale-orange oil (15.6 g, 46%).

1. filtrationThe resulting precipitate was filtered
2. washwashed with dioxane (100 mL), water (100 mL) and diethyl ether (100 mL)
3. customto give a white solid
4. temperatureThe reaction mixture was heated
5. temperatureto reflux
6. stirringstirred at that temperature for 20 hours
7. temperatureThe reaction was then cooled to room temperature
8. concentrationconcentrated in vacuo
9. additionWater (100 mL) was added
10. extractionThe aqueous layer was extracted into ethyl acetate (3×100 mL)
11. dry with materialthe combined organic extracts were dried over magnesium sulfate
12. concentrationconcentrated in vacuo

ORD record

ord-2b7a77296301440786cbee0a603a67ee

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278327B2