A kind of preparation method of eszopiclone
A technology of eszopiclone and zopiclone, which is applied in organic chemistry and other fields, can solve the problems of large consumption of organic solvents, insufficient mild reaction conditions, complicated operation, etc., to reduce production costs, reduce raw material costs, and simplify reaction steps Effect
Examples
Embodiment 1
[0038] The preparation of embodiment 1 eszopiclone-D-dibenzoyl tartrate
[0039] Experiment 1
[0040] Add 2.00g (5.14mmol) of zopiclone and 0.97g (2.58mmol) of D-dibenzoyltartaric acid monohydrate into 16ml of dichloromethane, stir to dissolve at room temperature (25°C), and slowly add 70ml of acetonitrile, Stir and crystallize at room temperature (25° C.) for 2 hours, filter and drain the precipitated solid, and dry at 80° C. for 12 hours to obtain 1.62 g of a white solid product (zopiclone-D-dibenzoyl tartrate) (yield 84.4 %, in the product, the left-handed product is 9.97%, the right-handed product is 90.03%, ee=80.0%).
[0041] Experiment 2
[0042] Add 2.00g (5.14mmol) of zopiclone to 180ml of acetonitrile, stir to dissolve at room temperature (8°C), and slowly add acetonitrile solution (8ml ), stirring and crystallizing at room temperature (8° C.) for 20 minutes after the addition was completed, the precipitated solid was filtered and drained, and dried at 80° C. for...
Embodiment 2
[0052] Example 2 Preparation of Crude Eszopiclone
[0053] Experiment 1
[0054] Add 500 mg of eszopiclone-D-dibenzoyl tartrate to a mixed solvent of ethyl acetate (30 ml) and water (10 ml), and slowly add saturation into 2N aqueous sodium hydroxide solution at room temperature until the pH value = 11 , stirred at room temperature for 0.5 hour, allowed to stand for liquid separation, the aqueous phase was extracted twice with 15 ml of ethyl acetate, the combined organic phases were washed with water, and the solvent was spin-dried to obtain 218 mg of crude dexzopic (yield 83.8%).
[0055] Experiment 2
[0056] Add 500 mg (1.29 mmol) of eszopiclone-D-dibenzoyl tartrate to a mixed solvent of dichloromethane (3 ml) and water (3 ml), and slowly add 1.5 g (10.8 mmol) of potassium carbonate in water at room temperature (1ml), stirred at room temperature for 1 hour, left to separate the liquids, the aqueous phase was extracted twice with 10ml of dichloromethane, the organic phases ...
Embodiment 3
[0061] The refining of embodiment 3 eszopiclone
[0062] Experiment 1
[0063] Add 10 g (ee=68.2%) of the crude product of eszopiclone into 400 ml of isopropyl acetate, heat to dissolve and then reflux for 0.5 hour, naturally cool down and crystallize under stirring, stir at room temperature for 2 hours, filter, drain, 90 After drying at °C for 8 hours, 7.0 g of refined eszopiclone was obtained (yield 70%, ee value 99.4%).
[0064] Experiment 2
[0065]Add 10 g (ee=68.2%) of the crude product of eszopiclone into 260 ml of ethyl acetate, heat to dissolve and then reflux for 0.5 hour, then naturally cool down to room temperature under stirring, stir and crystallize at room temperature for 2 hours, filter, and drain. Dry at 90°C for 6 hours to obtain 6.7 g of refined eszopiclone (67% yield, 99.4% ee value).
[0066] Experiment 3
[0067] Add 5 g (ee=68.2%) of the crude product of eszopiclone into dichloromethane (20 ml), stir until it dissolves, then slowly add isopropanol (5...
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Description
Claims
Application Information
- IPC
- C07D487/04
- Inventors
- 柯潇; 杜小春