Chemical Properties
Colorless to Light orange to Yellow clear liquid.
Uses
Ethyl 7-chloro-2-oxoheptanoate is a product of the Grignard reaction that can be used to synthesize organic compounds. It has been used in the preparation of pharmaceuticals such as cilastatin, which is used to inhibit cytochrome P450 enzymes in order to prolong the effectiveness of other drugs. This reagent also reacts with hydrochloric acid to form ethyl chloride and heptanoic acid, which can be used for chlorination reactions.
Uses
Ethyl 7-Chloro-2-oxoheptanoate is a reagent used in the synthesis of selective BCL-XL inhibitor A1155463 used in the treatment of cancer.
Preparation
Ethyl 7-chloro-2-oxoheptanoate is an organochlorine compound that is obtained by reacting ethyl chloride with magnesium in the presence of benzene and cilastatin as a catalyst.
Synthesis
The general procedure for the synthesis of ethyl 7-chloro-2-oxoheptanoate from 1-bromo-5-chloropentane and diethyl oxalate is as follows (Example 1):
1. Reaction apparatus preparation: the reaction apparatus 10 shown in Figure 1 was used, wherein the main flow channel 12 was a circular tube made of stainless steel, and the introduction points 12o and 12p were 180-degree T-shaped mixture flow channels.
2. Grignard reagent preparation: 1-bromo-magnesium-5-chloropentane Grignard reagent (0.45 mol/L) was prepared by adding magnesium powder to 1-bromo-5-chloropentane and diluted with tetrahydrofuran solvent, and the resulting diluted solution was used as feedstock M2.
3. Raw material preparation: Undiluted diethyl oxalate (7.4 mol/L) was used as raw material M1.
4. Reactant delivery: Feedstock M2 and feedstock M1 were delivered to a flow-type microfine reaction flow path 32 via smooth flow pumps 20 and 26 manufactured by TACMINA CORPORATION at flow rates of 110 mL/min and 5.1 mL/min, respectively.
5. Control of reaction conditions: Feedstock M2 (Grignard reagent) and feedstock M1 (diethyl oxalate) were controlled at 10 °C and room temperature, respectively, and the thermostatic liquid tank 28 was charged with methanol as refrigerant 30 and controlled at -15 °C.
6. Reaction process: Under the above conditions, the residence time of the reactants in the flow-type fine reaction flow channel 32 was about 14 seconds.
7. Product treatment: The liquid from the reaction was collected and the reaction was quenched with dilute hydrochloric acid to give the target product ethyl-7-chloro-2-pentyl oxalate in 90% yield.
References
[1] Patent: EP2065354, 2009, A1. Location in patent: Page/Page column 11-12
[2] Patent: WO2006/22511, 2006, A1. Location in patent: Page/Page column 10-11
