Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for preparing dicyclopropane methyl amine

A technology of dicyclopropylmethylamine and dicyclopropyl ketoxime, which is applied in the field of preparation of dicyclopropylmethylamine, can solve the problems of large safety hazards, cumbersome steps, and low yield, and achieve the reduction of waste water discharge and the process is green and environmentally friendly , cost reduction effect

Inactive Publication Date: 2015-06-03
成都塞恩斯医药科技有限公司
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The yield of the former is very low, only about 25%, and the application of metal sodium has great potential safety hazards, while the yield of the crude product reported by the latter is relatively high, reaching 75%, but the steps are cumbersome, the post-processing is complicated, and it consumes A large amount of absolute ethanol and a large amount of waste liquid are produced, and due to the water solubility of dicyclopropylmethylamine, the layering operation is actually unrealistic
[0003] CN102353710 discloses a high-temperature one-step route to generate dicyclopropylmethylamine, which makes dicyclopropyl ketone and ammonium formate react under reflux for a long time at 160-170°C to generate dicyclopropylmethylamine. Although this route saves the process steps, but has the following disadvantages: 1) The requirements for equipment conditions are very high, and the energy consumption is large; 2) Due to the high rigidity of the cyclopropyl ring, side reactions of three-membered ring opening will inevitably occur under high temperature conditions; 3) High temperature will also lead to partial oxidation of ketones, making the product mixed; 4) Dicyclopropylpropylamine is water-soluble, and in its patent, excessive ammonium formate is washed with water, and it is inevitable to wash a large amount of product into the solution, resulting in a low yield

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1 Preparation of dicyclopropyl ketoxime by oximation reaction

[0022] Take 110g of dicyclopropyl ketone and hydroxylamine hydrochloride (77g), add 200ml of water, and stir to dissolve. Then 500ml of 10wt% sodium bicarbonate aqueous solution was added dropwise, the temperature was controlled below 50°C, and the dropwise addition was completed in about 20 minutes. Then heat up to 60-80°C, stir for about 2 hours, and the reaction is complete. During the reaction process, a white solid was precipitated, and then the temperature was lowered to 0-5° C., and stirred for 2 hours, a large amount of white solid was precipitated. After suction filtration and drying, about 110 g of dicyclopropyl ketoxime was obtained with a yield of about 88%. 1 HNMR (Jeol, 400MHz, CDCl 3 ) data are as follows: δ0.60ppm (m, 4H, 2CH2); δ0.86ppm (m, 4H, 2CH2); δ0.97ppm (m, 1H, CH); δ2.40ppm (t, 1H, CH); δ8. 30ppm(s,1H,OH).

Embodiment 2

[0023] Example 2 Preparation of dicyclopropyl ketoxime by oximation reaction

[0024] Take hydroxylamine hydrochloride (77g), add 200ml of water, stir to dissolve. Then 500ml of 10wt% sodium hydroxide was added dropwise, the temperature was controlled below 50°C, and the dropwise addition was completed in about 20 minutes. Then, 110 g of dicyclopropyl ketone was added dropwise at 50° C.-55° C. for about 1.5 hours, and then continued to stir for about 1 hour, and the reaction was completed. During the reaction process, a white solid was precipitated, and then the temperature was lowered to 0-5° C., and stirred for 2 hours, a large amount of white solid was precipitated. After suction filtration and drying, about 115 g of dicyclopropyl ketoxime was obtained with a yield of about 92%.

Embodiment 3

[0025] Example 3 Preparation of Dicyclopropylmethylamine by Catalytic Hydrogenation

[0026] Add 100 g of dicyclopropyl ketoxime, 6 g of Raney nickel, and 350 ml of water into a 500 ml high-pressure hydrogenation kettle. Then nitrogen was replaced 3 times, and hydrogen was introduced. Control the hydrogen pressure in the reactor to 2Mpa, and the temperature to 70-80°C. After 4 hours, the reaction is complete. Discharge, cool, add 10g of sodium hydroxide to the mother liquor, stir, and suction filter to remove Raney nickel. Then extract three times with 200ml of dichloromethane, combine the dichloromethane solution, and distill. Collect 100mmHg, 100-110°C distillate, which is the product dicyclopropylmethylamine. A total of about 70 g of the product was obtained, with a yield of 74.2%. 1 HNMR (Jeol, 400MHz, DMSO-d6) data are as follows: δ0.15ppm (m, 4H, 2CH2); δ0.29ppm (m, 4H, 2CH2); δ1.56ppm (t, 1H, CH); δ5.74ppm (s,2H,NH2).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a method for preparing dicyclopropane methyl amine. The method comprises a step of performing catalytic hydrogenation on the dicyclopropane ketoxime and the hydrogen under the existence of a catalyst to generate the dicyclopropane methyl amine, wherein the raney nickel is taken as a catalyst in the catalytic hydrogenation and the process is performed in the water or the alkaline solution at the temperature of 30-90 DEG C. Compared with the current hydrogenation, the method has the advantages that a high-purity product with obviously increased yield can be obtained, the salt formation and dissociation process in an alcohol solvent can be avoided and the operation can be greatly simplified, besides, the costs of the solvent and the post-processing solvent can be greatly reduced, the wastewater discharge can be reduced and the process is green and environmentally friendly.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of dicyclopropylmethylamine. Background technique [0002] Dicyclopropylmethylamine is an important intermediate of the antihypertensive drug rilmenidine, which is widely used in the synthesis of medicines. The traditional synthetic method of dicyclopropylmethylamine mainly includes two steps, first, the oxime intermediate is generated by the oximation reaction of dicyclopropyl ketone and hydroxylamine hydrochloride, and then the hydrogenation reaction of the oxime intermediate produces dicyclopropylmethylamine . The reported oximation reactions are usually obtained by reacting with a base such as sodium bicarbonate and high temperature for a long time. For example, CN1629144A discloses that dicyclopropyl ketone and hydroxylamine hydrochloride are reacted in water at 150°C for 8 hours in the presence of sodium bicarbonate to prepare a...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07C211/17C07C209/40
Inventor 韩卫华黄松
Owner 成都塞恩斯医药科技有限公司