1,4-Dioxane → Methyl 2-chloro-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylate
Reaction equation
Br[C:2]1[C:7](=[O:8])[N:6]([CH3:9])[C:5]([Cl:10])=[C:4]([C:11]([O:13][CH3:14])=[O:12])[CH:3]=1.O1CCOC[CH2:16]1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:10][C:5]1[N:6]([CH3:9])[C:7](=[O:8])[C:2]([CH3:16])=[CH:3][C:4]=1[C:11]([O:13][CH3:14])=[O:12]Participants
Conditions
- Temperature
- 70 °C
Procedure
An oven dried two-necked flask was charged with methyl 5-bromo-2-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (5.79 g, 20.64 mmol), Pd(dppf)2Cl2 (0.82 g, 1.0 mmol) and dioxane (60 mL). The resulting red suspension was purged with argon for 10 min and ZnMe2 (2.0M, 10.3 mL, toluene) was added. The reaction mixture was stirred at 70° C. for 50 min, cooled at room temperature and quenched with MeOH (50 mL) and diluted with EtOAc (100 mL). The mixture was washed with a sat NH4Cl aq. solution, the organic layer was dried (Na2SO4) and concentrated under reduced pressure yielding to a brown residue. The residue was purified by flash chromatography (Biotage system) using a gradient of EtOAc (0-30%) in hexane to afford the title product (3.23 g, 73%).
Workup
- customThe resulting red suspension was purged with argon for 10 min
- additionZnMe2 (2.0M, 10.3 mL, toluene) was added
- temperaturecooled at room temperature
- customquenched with MeOH (50 mL)
- additiondiluted with EtOAc (100 mL)
- washThe mixture was washed with a sat NH4Cl aq. solution
- dry with materialthe organic layer was dried (Na2SO4)
- concentrationconcentrated under reduced pressure
- customyielding to a brown residue
- customThe residue was purified by flash chromatography (Biotage system)
Sources & evidence
- ORD record
- ord-288935b6a6484ea190b75d37e2118039
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673919B2
Reaction notes
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