Dynamic kinetic resolution method of 1-(1-naphthyl) ethylamine

A technology of dynamic kinetics and ethylamine, applied in the field of dynamic kinetics splitting of 1-ethylamine, can solve the problems of expensive resolving agent, many product side reactions, slow reaction rate, etc. The effect of high purity, fast reaction rate and great application value

Inactive Publication Date: 2012-03-28
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this classical 1-(1-naphthyl)ethylamine resolution method has disadvantages such as poor selectivity, many side reactions of products, ex

Method used

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  • Dynamic kinetic resolution method of 1-(1-naphthyl) ethylamine
  • Dynamic kinetic resolution method of 1-(1-naphthyl) ethylamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 1) Add p-chlorophenol, propionic acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine with a molar ratio of 1:1:1:0.03, stir and react for 7 hours, filter, dry the filtrate, concentrate, pass column, obtain p-chlorophenyl propionate as an acyl donor for subsequent use;

[0023] 2) Add palladium chloride and barium sulfate with a mass ratio of 1:6, heat in 80mL water at 80°C for 1h, add formaldehyde with a mass percentage concentration of 37% and a mass percentage concentration of 30% sodium hydroxide with a volume ratio of 1:1, 80 Heated at ℃ for 30 min, centrifuged, washed with water, dried overnight under low vacuum at 60 ℃, and the obtained solid was used as a racemic catalyst for later use;

[0024] 3) Add racemic 1-(1-naphthyl)ethylamine and p-chlorophenyl propionate, 20 mg / mL lipase and 40 mg racemic catalyst at a molar ratio of 1:1.05 in 3 mL of toluene and place in 30 mL stainless steel The reactor was hydrogenated, and the hydrogen pressure was 0.01MPa t...

Embodiment 2

[0026] 1) Add p-chlorophenol, n-butyric acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine in a molar ratio of 1:2:2:0.05, stir for 3 hours, filter, dry the filtrate, concentrate, Go through the column to obtain p-chlorophenyl n-butyrate as an acyl donor for subsequent use;

[0027] 2) Add palladium chloride and barium sulfate with a mass ratio of 1:6, heat in 80mL water at 80°C for 1h, add formaldehyde with a mass fraction of 37% and sodium hydroxide with a mass fraction of 30% at a volume ratio of 1:1, Heat at 100°C for 30 min, centrifuge, wash with water, and dry overnight under low vacuum at 60°C, and the obtained solid is used as a racemic catalyst for later use;

[0028] 3) In 3 mL of toluene, add 1-(1-naphthyl) ethylamine and p-chlorophenyl n-butyrate with a molar ratio of 1:1.3, 20 mg / mL lipase and 40 mg rac catalyst in 30 mL stainless steel The reactor was hydrogenated, and the hydrogen pressure was 0.1MPa to react for 15 hours, and the reaction temperature w...

Embodiment 3

[0030] 1) Add p-chlorophenol, n-valeric acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine with a molar ratio of 1:1.5:1.5:0.05, stir and react for 6 hours, filter, dry the filtrate, concentrate, Go through the column to obtain p-chlorophenyl valerate as an acyl donor for subsequent use;

[0031] 2) Add palladium chloride and barium sulfate with a mass ratio of 1:6, heat in 80mL water at 80°C for 1h, add formaldehyde with a mass fraction of 37% and sodium hydroxide with a mass fraction of 30% at a volume ratio of 1:1, Heat at 80°C for 30 min, centrifuge, wash with water, dry overnight under low vacuum at 60°C, and the obtained solid is used as a racemic catalyst for later use;

[0032] 3) In 3 mL of toluene, add racemic 1-(1-naphthyl)ethylamine and p-chlorophenyl pentanoate with a molar ratio of 1:1.05, 20 mg / mL lipase and 40 mg racemic catalyst in 30 mL stainless steel The reactor was hydrogenated, and the hydrogen pressure was 0.1MPa to react for 15 hours, and the r...

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Abstract

The invention discloses a dynamic kinetic resolution method for 1-(1-naphthyl) ethylamine, which comprises the following steps of: firstly, adding parachlorophenol, organic acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine, carrying out agitating reaction and filtering, drying, concentrating and carrying out column chromatography to obtain an acyl donor; or adding acetophenone and sodium borohydride, carrying out agitating reaction, depressurizing and distilling, washing, extracting, drying and concentrating to obtain phenethyl alcohol, adding the phenethyl alcohol, acetyl chloride and triethylamine, carrying out agitating reaction and washing, drying, concentrating and carrying out column chromatography to obtain an acyl donor; secondly, adding palladium salt and a carrier, heating, adding formaldehyde and sodium hydroxide, heating and centrifuging, washing and vacuum-drying to obtain a racemic catalyst for standby; and thirdly, adding the 1-(1-naphthyl) ethylamine in methyl benzene, the acyl donor, lipase and the racemic catalyst and carrying out hydrogenation reaction to obtain amide. The dynamic kinetic resolution method has high reaction speed, lower temperature, high conversion rate and product optical purity and great application value.

Description

field of invention [0001] The invention relates to a dynamic kinetic resolution method, in particular to a dynamic kinetic resolution method for 1-(1-naphthyl)ethylamine. Background technique [0002] Cinacalcet hydrochloride, chemical name (α R )-α-Methyl- N -[3-[3-(Trifluoromethyl)phenyl]propyl]-1-naphthylmethylamine hydrochloride, the first drug in a new class of compounds known as calcimimetics, capable of Activates calcium receptors in the parathyroid glands, thereby reducing parathyroid hormone (PTH) secretion. First launched in the United States in 2004, it is clinically used to treat hypercalcemia in patients with secondary hyperparathyroidism and parathyroid tumors caused by chronic kidney disease receiving dialysis. It can inhibit the secretion of parathyroid hormone by activating calcium ion receptors. It is well absorbed in the body and has good bioavailability (about 80%). It reaches the maximum blood concentration 3 hours after taking it, and it has long-ter...

Claims

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Application Information

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IPC IPC(8): C12P41/00C12P13/00C12P13/02
Inventor 符思敏徐刚吴坚平杨立荣
Owner ZHEJIANG UNIV
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