Methanol → (3-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)-acetonitrile

To a suspension of potassium tert-butoxide (8.95 g, 79.9 mmol) in DME (250 mL)-78° C. under nitrogen was added a solution of 1-(isocyanomethyl sulfonyl)-4-methyl benzene (9.36 g, 47.94 mmol) in DME (50 ml). After stirring for 10 minutes, a solution of 3-cyclopropyl-1-methyl-1H-pyrazole-4-carbaldehyde (6 g, 39.95 mmol) in DME (100 mL) was added. The resulting mixture was allowed to stir at −78° C. for 1 hour and then at room temperature for 1 hour. Methanol (50 mL) was added and the resulting mixture refluxed for 1 hour. The reaction mixture was quenched with saturated ammonium chloride solution (200 mL) and extracted with EtOAc (2×200 mL). The combined organic layers were washed with brine (2×50 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with hexane:EtOAc 90:10 to afford the title compound an off-white solid in 67% yield, 4.3 g.

1. stirringto stir at −78° C. for 1 hour
2. waitat room temperature for 1 hour
3. temperaturethe resulting mixture refluxed for 1 hour
4. customThe reaction mixture was quenched with saturated ammonium chloride solution (200 mL)
5. extractionextracted with EtOAc (2×200 mL)
6. washThe combined organic layers were washed with brine (2×50 mL)
7. dry with materialdried over sodium sulphate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude material was purified by silica gel column chromatography
11. washeluting with hexane:EtOAc 90:10

ORD record

ord-4347aef502c14c0790824728a5eb45f7

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846698B2