Isopropyl iodide → Ethyl 1-(1-methylethyl)-1H-pyrazole-5-carboxylate

Temperature

20 °C

To a solution of ethyl 1H-pyrazole-5-carboxylate (1 g) (for example, available form Bio-Farma) in acetonitrile (80 ml) was added cesium carbonate (2.32 g). 20 min later 2-iodopropane (0.714 ml) was added and the mixture stirred under nitrogen at 20° C. for 18 h. 2-Iodopropane (0.714 ml) was added and the mixture stirred under nitrogen at 20° C. for 5 h. Then further 2-iodopropane (0.714 ml) was added and the mixture was stirred at 20° C. for 18 h. The solvent was removed in vacuo and the residue was partitioned between water (30 ml) and DCM (30 ml). The aqueous phase was extracted with DCM (2×20 ml) and separated by hydrophobic frit. The combined organic layers were concentrated in vacuo. Purification of the residue by chromatography on silica gel (70 g silica), eluting with a gradient of 0-100% ethyl acetate in cyclohexane over 30 min gave the title compound (513 mg) as a yellow oil.

1. stirringthe mixture stirred under nitrogen at 20° C. for 5 h
2. stirringthe mixture was stirred at 20° C. for 18 h
3. customThe solvent was removed in vacuo
4. customthe residue was partitioned between water (30 ml) and DCM (30 ml)
5. extractionThe aqueous phase was extracted with DCM (2×20 ml)
6. customseparated by hydrophobic frit
7. concentrationThe combined organic layers were concentrated in vacuo
8. customPurification of the residue by chromatography on silica gel (70 g silica)
9. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane over 30 min

ORD record

ord-1b621e9f15954dcdbce316bad1dafe54

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658635B2