Ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate → HCID 178469202, compound

Temperature

40 °C

In a 10 L reaction vessel, pyridinium p-toluenesulfonic acid (39.7 g, 158 mMol) was added to a stirred solution of ethyl-2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (Preparation 1) and ethyl-3-ethoxybut-2-eneoate (Preparation 2) in toluene (6.0 L) at room temperature under argon. The resulting mixture was heated to reflux, and stirred at reflux for 6 hours. The mixture was cooled 40° C. and stirred at 40° C. for 16 hours. The mixture was heated to 50° C. (to dissolve the precipitate) and the solution was run out of the reaction vessel. The reaction vessel was charged with 21% (w/w) sodium ethoxide in ethanol (1.1 L, 3.48 Mol) and ethanol (2.0 L), and the resulting mixture was heated to 50° C. The reaction mixture was then poured back into the reaction vessel over 5 minutes. The resulting mixture was heated to reflux and stirred at reflux for 2 hours. The mixture was cooled to 30° C. and split into 2 approximately equal batches. Each batch was treated with Celite® (approx. 2 L) and concentrated under reduced pressure. The resulting solids were suspended in water (2.0 L, 40° C.) and stirred vigorously until all solids were free flowing. The solids were collected by filtration through a pad of Celite®, and the filter-cake was washed with water (2.5 L, 40° C.). The filtrate was washed with diethylether (2×1.3 L) and then cooled to 15° C. 6 M hydrochloric acid was added carefully until pH 4 was achieved. The resulting precipitate was collected by filtration and the filter-cake was washed with dilute hydrochloric acid (500 mL). The filter-cake was dried in a drying oven, at 50° C. for 2 days. This gave the title compound as a yellow solid (584 g, 64%).

1. temperatureThe resulting mixture was heated
2. temperatureto reflux
3. temperatureat reflux for 6 hours
4. stirringstirred at 40° C. for 16 hours
5. temperatureThe mixture was heated to 50° C. (
6. dissolutionto dissolve the precipitate) and the solution
7. temperaturethe resulting mixture was heated to 50° C
8. additionThe reaction mixture was then poured back into the reaction vessel over 5 minutes
9. temperatureThe resulting mixture was heated
10. temperatureto reflux
11. stirringstirred
12. temperatureat reflux for 2 hours
13. temperatureThe mixture was cooled to 30° C.
14. customsplit into 2 approximately equal batches
15. additionEach batch was treated with Celite® (approx. 2 L)
16. concentrationconcentrated under reduced pressure
17. customwere suspended in water (2.0 L, 40° C.)
18. stirringstirred vigorously until all solids
19. filtrationThe solids were collected by filtration through a pad of Celite®
20. washthe filter-cake was washed with water (2.5 L, 40° C.)
21. washThe filtrate was washed with diethylether (2×1.3 L)
22. temperaturecooled to 15° C
23. addition6 M hydrochloric acid was added carefully until pH 4
24. filtrationThe resulting precipitate was collected by filtration
25. washthe filter-cake was washed with dilute hydrochloric acid (500 mL)
26. customThe filter-cake was dried in a drying oven, at 50° C. for 2 days

ORD record

ord-31ede2ef067643a294ccc35ecef20430

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809363B2