1,4-Dioxane → Ethyl 3,5-diethylpyridine-4-carboxylate
Reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6](Br)[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:14]([Zn]CC)[CH3:15].O1CCO[CH2:21][CH2:20]1>>[CH2:14]([C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:20][CH3:21])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:15]Participants
Conditions
- Temperature
- 70 °C
Procedure
To a solution of ethyl 3,5-dibromopyridine-4-carboxylate (5.98 g, 19.35 mmol) in anhydrous dioxane (40 mL) was added at room temperature (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium (II) (424 mg, 0.580 mmol). Diethylzinc (3.58 g, 23.8 mL, 28.95 mmol, 15% solution in toluene) was then added dropwise. The reaction mixture was heated at 70° C. for 45 minutes, then cooled to room temperature and quenched with MeOH. The resulting mixture was extracted with ethyl acetate (2×100 mL), washed with water, 0.1 N HCl, and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated, and the residue was purified by CombiFlash using 0-30% ethyl acetate in hexane to provide ethyl 3,5-diethylpyridine-4-carboxylate as a pale yellow oil (2.2 g, 54.8% yield); 1H NMR (400 MHz, CDCl3): δ 1.23 (t, 6H), 1.40 (t, 3H), 2.64 (q, 4H), 4.44 (q, 2H), 8.36 (s, 2H), M+208.5; M+180.2.
Workup
- temperaturecooled to room temperature
- customquenched with MeOH
- extractionThe resulting mixture was extracted with ethyl acetate (2×100 mL)
- washwashed with water, 0.1 N HCl, and brine
- dry with materialThe organic layer was dried over anhydrous sodium sulfate
- filtrationfiltered
- customThe filtrate was evaporated
- customthe residue was purified by CombiFlash
Sources & evidence
- ORD record
- ord-48dff454431a402fa6171bebff39630d
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315521B2
Reaction notes
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