Preparation method of caine drug intermediate (S)-2-piperidinecarboxylic acid
A technology of piperidinecarboxylic acid and cyanopiperidine is applied in the field of preparation of caine-type drug intermediate-2-piperidinecarboxylic acid, which can solve the problems such as difficulty in obtaining starting materials, high production cost, complicated steps, etc. Mild conditions, improved safety, and good reaction yield
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Examples
Embodiment 1
[0044] The synthesis of embodiment 1 compound I
[0045] Add 1g (8.3mmol) of 5-chlorovaleraldehyde, 1.25g (9.13mmol) of L-phenylglycinol, and 1g (10mmol) of trimethylsilylcyanide into the reaction flask, and then add 115mg (0.415mmol) of magnesium diiodide , Stir the reaction at room temperature (25° C.) for 4 h. TLC monitors the reaction process. After the reaction is completed, the reaction solution is purified by silica gel column chromatography. The eluent is sherwood oil: ethyl acetate (volume ratio: 5: 1), and after concentration, 209 mg of light yellow oily product I is obtained. The yield is 95%. HPLC area normalization method detection purity is 98% [chromatographic condition: chromatographic column Kromasil C 18Column (4.6mm×250mm, 5μm), mobile phase: acetonitrile-water (volume ratio 70:30), detection wavelength: 254nm, column temperature: 25°C, flow rate: 1.0mL·min -1 ]. Optical purity 98% [chromatographic conditions: chiral chromatographic column CHIRALPAK AD-H...
Embodiment 2
[0046] The synthesis of embodiment 2 compound I
[0047] Add 1g (8.3mmol) of 5-chlorovaleraldehyde, 1.25g (9.13mmol) of L-phenylglycinol, and 1g (10mmol) of trimethylsilylcyanide into the reaction flask, and then add 76mg (0.415mmol) of magnesium dibromide , Stir the reaction at room temperature (25° C.) for 6 h. TLC monitors the reaction process. After the reaction is completed, the reaction solution is purified by silica gel column chromatography. The eluent is sherwood oil: ethyl acetate (volume ratio: 5: 1). After concentration, 171 mg of the light yellow oily product I is obtained. The yield is 78%. HPLC area normalization method detection purity is 98% [chromatographic condition: chromatographic column Kromasil C 18 Column (4.6mm×250mm, 5μm), mobile phase: acetonitrile-water (volume ratio 70:30), detection wavelength: 254nm, column temperature: 25°C, flow rate: 1.0mL·min -1 ]. Optical purity 98% [chromatographic conditions: chiral chromatographic column CHIRALPAK AD-...
Embodiment 3
[0048] The synthesis of embodiment 3 compound I
[0049] Add 1g (8.3mmol) of 5-chlorovaleraldehyde, 1.25g (9.13mmol) of L-phenylglycinol, and 1.2g (12mmol) of trimethylsilylcyanide into the reaction flask, and then add 186mg (0.8mmol) of magnesium perchlorate ), stirred at room temperature (25° C.) for 8 h. TLC monitors the reaction process. After the reaction is completed, the reaction solution is purified by silica gel column chromatography. The eluent is sherwood oil: ethyl acetate (volume ratio: 5: 1), and after concentration, 158 mg of light yellow oily product I is obtained. 72%. HPLC area normalization method detection purity is 98% [chromatographic condition: chromatographic column Kromasil C 18 Column (4.6mm×250mm, 5μm), mobile phase: acetonitrile-water (volume ratio 70:30), detection wavelength: 254nm, column temperature: 25°C, flow rate: 1.0mL·min -1 ]. Optical purity 97% [chromatographic conditions: chiral chromatographic column CHIRALPAK AD-H (250mm×4.6mm, 5μm...
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Abstract
Description
Claims
Application Information
- IPC
- C07D211/60
- CPC
- C07D211/60
- Inventors
- 杨玉燕; 张兴贤