Ethoxalyl chloride → Ethyl 2-(3-chloro-4-(methylthio)phenyl)-2-oxoacetate
Reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].Cl[C:6](=[O:12])[C:7]([O:9][CH2:10][CH3:11])=[O:8].[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][CH3:21]>C(Cl)(Cl)Cl>[CH2:10]([O:9][C:7](=[O:8])[C:6]([C:18]1[CH:17]=[CH:16][C:15]([S:20][CH3:21])=[C:14]([Cl:13])[CH:19]=1)=[O:12])[CH3:11]Participants
Conditions
- Temperature
- 0 °C
Procedure
A solution of aluminum trichloride (34.8 g, 261.4 mmol) in chloroform (120 mL) cooled to 0° C. was treated with a solution of ethyl chlorooxoacetate (18.7 mL, 167.5 mmol) in chloroform (120 mL). The mixture was stirred at 0° C. for 30 min. At this time, a solution of 2-chlorothioanisole (25.0 g, 156.5 mmol) in chloroform (120 mL) was added dropwise to the reaction mixture. It was then allowed to warm to 25° C. and stirred for an additional 3.5 h at 25° C. At this time, the reaction was quenched by the slow addition of water (500 mL) and extracted with chloroform (3×50 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded (3-chloro-4-methylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (31.37 g, 77%) as a yellow oil: EI-HRMS m/e calcd for C18H24Cl2N2O3 (M+) 386.1164, found 386.1154.
Workup
- temperatureto warm to 25° C.
- stirringstirred for an additional 3.5 h at 25° C
- customAt this time, the reaction was quenched by the slow addition of water (500 mL)
- extractionextracted with chloroform (3×50 mL)
- dry with materialThe organics were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-8f6a666ef0964757bc8454e86f29ced2
- Source dataset
- uspto-grants-2003_03
- Patent number
- US06528543B1
Reaction notes
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