Acetic Acid → 2-Chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([F:15])[C:5]([C:8](=[O:14])[CH:9](C)[C:10](O)=O)=[N:6][CH:7]=1.C(O)(=O)C.[Cl:20]Cl>O>[Cl:20][CH:9]([CH3:10])[C:8]([C:5]1[C:4]([F:15])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=1)=[O:14]Participants
Procedure
20.8 g of 3-(5-chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid (Example P35) are introduced into 125 ml of glacial acetic acid. 6.3 g of chlorine gas are introduced into the solution in the course of 1 hour . The mixture is then poured into 700 ml of water and extracted with tert-butyl methyl ether. The combined ethereal phases a rewashed with water and dried over magnesium sulfate, filtered and concentrated by evaporation in vacuo. The crude product is dissolved in 180 ml of tert-butyl methyl ether, 45 g of silica gel are added and the mixture is stirred for 30 minutes, in the course of which the evolution of gas observed initially comes to a halt. The silica gel is then filtered off and subsequently washed and the combined ethereal phases are concentrated to dryness in vacuo. 20.1 g of an oily crude product are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 411 (v/v)). 17.0 g of the desired title compound are obtained in the form of a solid having a melting point of 29-32° C.
Workup
- extractionextracted with tert-butyl methyl ether
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated by evaporation in vacuo
- dissolutionThe crude product is dissolved in 180 ml of tert-butyl methyl ether
- addition45 g of silica gel are added
- filtrationThe silica gel is then filtered off
- washsubsequently washed
- concentrationthe combined ethereal phases are concentrated to dryness in vacuo
Sources & evidence
- ORD record
- ord-062257bce9f6411fb526fe4411f9e0d9
- Source dataset
- uspto-grants-2001_08
- Patent number
- US06274536B1
Reaction notes
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