Nicotinic Acid → Ethyl 3-oxo-3-(pyridin-3-yl)propanoate
Reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C(C1NC=CN=1)(C1NC=CN=1)=O.[Mg+2].[Cl-].[Cl-].[K+].[C:26]([O:32][CH2:33][CH3:34])(=[O:31])[CH2:27]C([O-])=O.[N-]1C=CN=C1>O1CCCC1>[O:9]=[C:1]([C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)[CH2:27][C:26]([O:32][CH2:33][CH3:34])=[O:31]Participants
Procedure
To a suspension of nicotinic acid 5.00 g (40.6 mmol) in tetrahydrofuran 50 mL was added carbonyl diimidazole 9.76 g (60.9 mmol) at 5° C. and stirred at room temperature for 1 hour. In a separate flask, a suspension of MgCl2 4.64 g (48.7 mmol) and ethyl malonate potassium salt 10.37 g (60.92 mmol) in tetrahydrofuran 50 mL was stirred at 50° C. for 4 hours. To this suspension was added the aforementioned imidazolide solution at room temperature and stirred for 12 hours. The reaction was quenched by the addition of water and extracted into ethyl acetate. The organic layer was washed by brine, dried over MgSO4, filtrated and the solvent was evaporated. Silica gel chromatography (n-hexane/AcOEt=2/1) afforded the title compound 3.89 g as pale yellow oil. Yield 49.5%.
Workup
- stirringwas stirred at 50° C. for 4 hours
- stirringstirred for 12 hours
- customThe reaction was quenched by the addition of water
- extractionextracted into ethyl acetate
- washThe organic layer was washed by brine
- dry with materialdried over MgSO4
- filtrationfiltrated
- customthe solvent was evaporated
Sources & evidence
- ORD record
- ord-52e00cba3a7b469181a511ba17c706ed
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08129386B2
Reaction notes
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