Hydrochloric Acid → 1-(2-ethoxyethyl)-3-ethyl-4-nitro-1H-pyrazole-5-carboxamide

A 1 L flask was charged with 3-ethyl-4-nitropyrazole-5-carboxamide (prepared as described in EP 1176142 at page 18) (15.0 g, 81 mmol), triphenylphosphine (25.6 g, 97.8 mmol), and tetrahydrofuran (120 mL). The resulting mixture was cooled by placing the flask in a 0° C. bath and 2-ethoxyethanol (9.5 ml, 98 mmol) was added to the flask. A solution of di-tert-butyl azodicarboxylate (22.5 g, 97.8 mmol) in tetrahydrofuran (90 mL) was then added to the flask over a period of 2.5 hours. The mixture was stirred with cooling for an additional hour and then warmed to room temperature and stirred for one additional hour. The mixture was again cooled to 0° C., treated with 6M hydrochloric acid (40 ml), and heated to 40° C. for one hour. The mixture was partially concentrated and extracted between ethyl acetate and water. The aqueous layer was back-extracted with ethyl acetate. The combined organic layers were washed with water, washed with brine, dried over magnesium sulfate, filtered and then concentrated. The resulting viscous oil was treated with 2-propanol and this mixture was then concentrated. The resulting material was treated with 2-propanol and heated. Upon cooling, the resulting crystals were filtered, rinsed with cold 2-propanol, and dried to afford 16.5 g of the title compound.

1. temperatureThe resulting mixture was cooled
2. customin a 0° C.
3. temperaturewith cooling for an additional hour
4. stirringstirred for one additional hour
5. temperatureThe mixture was again cooled to 0° C.
6. temperatureheated to 40° C. for one hour
7. concentrationThe mixture was partially concentrated
8. extractionextracted between ethyl acetate and water
9. extractionThe aqueous layer was back-extracted with ethyl acetate
10. washThe combined organic layers were washed with water
11. washwashed with brine
12. dry with materialdried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated
15. additionThe resulting viscous oil was treated with 2-propanol
16. concentrationthis mixture was then concentrated
17. additionThe resulting material was treated with 2-propanol
18. temperatureheated
19. temperatureUpon cooling
20. filtrationthe resulting crystals were filtered
21. washrinsed with cold 2-propanol
22. customdried

ORDレコード

ord-89c7f447b8cd4c87814e7da4178cef39

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08518956B2