Isoamyl Nitrite → 5-[4-(benzyloxy)phenyl]-3-chloro-1-(4-methoxyphenyl)-1H-pyrazole

A mixture of 5-[4-(benzyloxy)phenyl]-3-amino-1-(4-methoxyphenyl)-1H-pyrazole (4.0 g), lithium chloride (2.28 g), and copper(II) chloride (2.90 g) in acetonitrile (50 ml) was stirred at ambient temperature for 10 minutes. To this mixture was added isoamyl nitrite (2.52 g), and the mixture was stirred at ambient temperature for 1.5 hours. To the reaction mixture was added a mixture of ethyl acetate and saturated aqueous ammonium chloride solution. The mixture was stirred at ambient temperature for a while, and partitioned. The aqueous layer was reextracted with ethyl acetate. The combined organic layers were washed with saturated aqueous ammonium chloride solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 20% AcOEt/n-hexane. The pure fractions were collected and concentrated in vacuo to give 5-[4-(benzyloxy)phenyl]-3-chloro-1-(4-methoxyphenyl)-1H-pyrazole (2.81 g) as a solid.

1. stirringthe mixture was stirred at ambient temperature for 1.5 hours
2. additionTo the reaction mixture was added
3. stirringThe mixture was stirred at ambient temperature for a while
4. custompartitioned
5. washThe combined organic layers were washed with saturated aqueous ammonium chloride solution and saturated aqueous sodium chloride solution
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel column chromatography
9. washeluted with 20% AcOEt/n-hexane
10. customThe pure fractions were collected
11. concentrationconcentrated in vacuo

ORD record

ord-01cb74ecaa10412f8af73bbe5ec45c84

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07183306B2