Dimethyl Sulfate → Ethyl 4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate
Reaction equation
[Cl:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4](Cl)[CH:3]=1.S([O:19][CH3:20])(OC)(=O)=O>C(#N)C.C(=O)(O)[O-].[Na+].O>[CH2:11]([O:10][C:8]([C:7]1[C:2]([Cl:1])=[CH:3][C:20](=[O:19])[N:5]([CH3:4])[CH:6]=1)=[O:9])[CH3:12]Participants
Conditions
- Temperature
- 120 °C
Procedure
Ethyl 4,6-dichloronicotinate [prepared according to the literature procedure of J. Chem. Soc. 5163 (1963)] (3.19 g, 14.5 mmol) and dimethyl sulfate (6.0 mL, 63 mmol) were combined in a thick-walled glass tube with a Teflon cap. The tube was sealed and heated in a 120° C. sand bath. After 5 h, the reaction was cooled to ambient temperature and diluted with acetonitrile (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The reaction mixture was stirred vigorously overnight (ca. 18 h). This mixture was further diluted with water and extracted with dichloromethane (3×). The combined extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to afford 4-chloro-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid ethyl ester (2.65 g, 85% yield) as an oil that solidified upon standing.
Workup
- customcap
- customThe tube was sealed
- temperaturethe reaction was cooled to ambient temperature
- extractionextracted with dichloromethane (3×)
- washThe combined extracts were washed with brine
- dry with materialdried over anhydrous magnesium sulfate
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-fa2f21dc32a340cba478e1aed4a40b6d
- Source dataset
- uspto-grants-2007_09
- Patent number
- US07273877B2
Reaction notes
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