N-bromobutanimide → Methyl 5-bromo-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[N:12]([CH3:22])[C:13](=[O:21])[CH:14]=[CH:15][C:16]=1[C:17]([O:19][CH3:20])=[O:18].[Br:23]N1C(=O)CCC1=O>>[Br:23][C:14]1[C:13](=[O:21])[N:12]([CH3:22])[C:11]([NH:10][C:3]2[CH:4]=[CH:5][C:6]([S:8][CH3:9])=[CH:7][C:2]=2[F:1])=[C:16]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=1Participants
3
Procedure
To a solution of methyl 2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate was added N-bromosuccinimide. The reaction mixture was stirred at room temperature for 25 minutes and then quenched with saturated sodium bisulfite. The reaction mixture was diluted with H2O and partitioned between EtOAc/diethyl ether and saturated NaCl. The layers were separated and the aqueous layer was reextracted with EtOAc (1×). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/EtOAc, 15:1) gave methyl 5-bromo-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate.
Workup
- customquenched with saturated sodium bisulfite
- additionThe reaction mixture was diluted with H2O
- custompartitioned between EtOAc/diethyl ether and saturated NaCl
- customThe layers were separated
- dry with materialThe combined organic layers were dried (Na2SO4)
- concentrationconcentrated under reduced pressure
- customPurification by flash column chromatography (methylene chloride/EtOAc, 15:1)
Sources & evidence
- ORD record
- ord-afe56547c4b847d6b150f74ab47e6c59
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08299076B2
Reaction notes
Loading…