Hydrochloric Acid → 5-chloro-1-[2-(2-methoxyethoxy)-ethyl]-1H-pyrazole-4-carboxylic acid ethyl ester

To a mixture of t-butyl nitrite (8.5 mL, 64.5 mmol), anhydrous cuprous chloride (6.54 g, 66.1 mmol) and anhydrous acetonitrile (80 mL) was added 5-amino-1-[2-(2-methoxyethoxy)-ethyl]-1H-pyrazole-4-carboxylic acid ethyl ester (10.38 g, 40.3 mmol) over 10 minutes at 0° C. The reaction mixture was stirred at room temperature for 1 h, then at 70° C. for 2 h. The mixture was then cooled to room temperature and poured carefully into 6.0 N aqueous HCl (45 mL). The aqueous phase was extracted with methylene chloride (3×150 mL). The combined organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to provide the crude material as an oil. The product was purified by column chromatography on silica gel (eluting with ethyl acetate/hexanes, using a gradient of 1:3 to 1:0) to provide 5-chloro-1-[2-(2-methoxyethoxy)-ethyl]-1H-pyrazole-4-carboxylic acid ethyl ester as a light yellow oil (3.43 g, 30%). Mass spectrum: m/z: 277.0 (M+1).

1. waitat 70° C. for 2 h
2. temperatureThe mixture was then cooled to room temperature
3. extractionThe aqueous phase was extracted with methylene chloride (3×150 mL)
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto provide the crude material as an oil
8. customThe product was purified by column chromatography on silica gel (
9. washeluting with ethyl acetate/hexanes

ORD-Eintrag

ord-35067dcc8b9048838bc6cd33a0cb6e29

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07728029B2