Tetronic acid → 4-[[(6-Chloro-5-fluoropyridin-3-yl)methyl](2,2-difluoroethyl)amino]furan-2(5h)-one
Reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][CH2:10][CH:11]([F:13])[F:12])=[CH:4][C:3]=1[F:14].[CH2:15]1[C:20](=[O:21])[O:19][CH2:18][C:16]1=O>C(O)(=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:10][CH:11]([F:13])[F:12])[C:16]2[CH2:18][O:19][C:20](=[O:21])[CH:15]=2)=[CH:4][C:3]=1[F:14]Participants
Procedure
317 mg (1.41 mmol) of N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamine (III-1) are added to 173 mg (1.69 mmol) of tetronic acid in 400 μA of acetic acid, and the mixture is stirred at room temperature for 6 hours. The reaction mixture is concentrated under reduced pressure, and the residue is then partitioned between dichloromethane and water. The aqueous phase is extracted two more times with dichloromethane. The combined organic phases are washed with 1 N aqueous sodium hydroxide solution and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (silica gel 60-Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture ethyl acetate:cyclohexane (3:1) gives 316 mg (64% of theory) of 4-[[(6-chloro-5-fluoropyridin-3-yl)methyl](2,2-difluoroethyl)amino]furan-2(5H)-one.
Workup
- concentrationThe reaction mixture is concentrated under reduced pressure
- customthe residue is then partitioned between dichloromethane and water
- extractionThe aqueous phase is extracted two more times with dichloromethane
- washThe combined organic phases are washed with 1 N aqueous sodium hydroxide solution
- concentrationconcentrated under reduced pressure
- customPurification of the residue by column chromatography on silica gel (silica gel 60-Merck, particle size: 0.04 to 0.063 mm)
Sources & evidence
- ORD record
- ord-7f31bd0ea6244e2099aa00aa273df80c
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08084452B2
Reaction notes
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