Ethanol → 3-(3-Fluoro-5-chloro-2-pyridyl)-5-ethoxycarbonyl-1-methyl-[1H]-pyrazole
Reaction equation
[F:1][C:2]1[C:3]([C:9]2[CH:13]=[C:12](Br)[N:11]([CH3:15])[N:10]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.C(N([CH2:21][CH3:22])CC)C.[C]=[O:24].[CH2:25]([OH:27])C>>[F:1][C:2]1[C:3]([C:9]2[CH:13]=[C:12]([C:25]([O:27][CH2:21][CH3:22])=[O:24])[N:11]([CH3:15])[N:10]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1Participants
Conditions
- Temperature
- 22 °C
Procedure
5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole (Example H40) are initially introduced into an autoclave together with 7.2 ml of triethylamine, 0.48 g of bis-triphenylphosphinepalladium dichloride (PdCl2(PPh3)2) and 70 ml of absolute ethanol. 100 bar of carbon monoxide are forced in at 22° C. and the mixture is then kept at 100° C. for 48 hours. In the meantime, a further 0.48 g of bis-triphenylphosphinepalladium dichloride is added. The mixture is then cooled to 22° C. and the pressure is released. The resulting reaction mixture is filtered over Hyflo and—after removal of the ethanol—taken up in ethyl acetate. The ethyl acetate phase is washed with dilute hydrochloric acid and then with brine, dried over sodium sulfate, filtered and concentrated in vacuo. 3.17 g of a brown solid are obtained, and this gives, after purification over a silica gel flash column (eluting agent: n-hexane/ethyl acetate 2/1), 2.31 g of the desired title compound as a pale yellow solid of melting point 117-118° C.
Workup
- customare forced in at 22° C.
- customThe resulting reaction mixture
- filtrationis filtered over Hyflo
- custom—after removal of the ethanol—
- washThe ethyl acetate phase is washed with dilute hydrochloric acid
- dry with materialwith brine, dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-08fe4ffd60fc4ed9bf88b07cb132dc0e
- Source dataset
- uspto-grants-2001_03
- Patent number
- US06204221B1
Reaction notes
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