Sulfuric Acid → ethyl 3-iodo-5-methyl-1H-pyrazole-4-carboxylate

Temperature

0 °C

Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate (2.1 g, 12.41 mmol, 1.00 equiv) was added in portions to a solution of sulfuric acid (98%, 6 mL) in 5 mL water at 0° C. The resulting solution was stirred at 0° C. for 30 min. A solution of sodium nitrite (1.28 g, 18.55 mmol, 1.49 equiv) in 5 mL water was added dropwise to the reaction mixture at 0° C. The resulting solution was stirred at 0° C. for another hour. A solution of potassium iodide (4.2 g) in 5 mL water was then added dropwise. The resulting solution was stirred at 25° C. for 8 h. The reaction mixture was extracted with 2×50 mL of ethyl acetate. The combined organic layers was washed sequentially with 1×100 mL of saturated Na2SO3 solution and 2×100 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-30% of ethyl acetate in petroleum ether to give 2.1 g (60%) of ethyl 5-iodo-3-methyl-1H-pyrazole-4-carboxylate as a yellow solid. 1H-NMR (300 MHz, CDCl3): δ4.32 (q, J=7.2 Hz, 2H), 2.61 (s, 3H), 1.38 (t, J=7.2 Hz, 3H) ppm. LCMS (method D, ESI): RT=1.24 min, m/z=281.0 [M+H]+.

1. stirringThe resulting solution was stirred at 0° C. for another hour
2. stirringThe resulting solution was stirred at 25° C. for 8 h
3. extractionThe reaction mixture was extracted with 2×50 mL of ethyl acetate
4. washThe combined organic layers was washed sequentially with 1×100 mL of saturated Na2SO3 solution and 2×100 mL of brine
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. concentrationconcentrated under vacuum
7. customThe residue was purified on a silica gel column
8. washeluted with 0-30% of ethyl acetate in petroleum ether

ORD record

ord-7878e43830084daa9897ec9952751550

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952026B2