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The preparation method of 1-benzyl-3-piperidone hydrochloride

A technology of piperidone hydrochloride and benzylglycine ethyl ester is applied in the field of preparation of 1-benzyl-3-piperidone hydrochloride, can solve the problem of high cost, achieve good quality, short synthesis steps, high purity effect

Active Publication Date: 2018-06-01
CHONGQING WEIPENG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The hydrogenation reduction step of the preparation method uses high-cost noble metal catalysts such as platinum dioxide and platinum carbon, and the starting material 3-hydroxypyridine and the catalyst cause the cost of this route to be too high

Method used

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  • The preparation method of 1-benzyl-3-piperidone hydrochloride
  • The preparation method of 1-benzyl-3-piperidone hydrochloride
  • The preparation method of 1-benzyl-3-piperidone hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Embodiment 1 prepares 1-benzyl-3-piperidone hydrochloride

[0035] Follow the steps below:

[0036] (1) Preparation of Intermediate IV

[0037] 43g (0.4mol) of benzylamine, 250mL of acetonitrile, 13.3g (0.04mol) of tetrabutylammonium hydrogen sulfate, and 40.4g (0.4mol) of triethylamine were added successively to a 1000mL three-necked flask. A solution of 49g (0.4mol) of ethyl acetate and 150mL of acetonitrile, keep it warm at 25-28°C for 4h after dropping, HPLC detects that the reaction is complete, cool the reaction solution to 0-5°C and let it stand for 1.5h, filter, and depressurize the filtrate Concentrate to obtain 80.5 g (104% yield) of a light brown oily substance (ie Intermediate IV), with a purity of 98.2% as detected by HPLC, which is directly put into the next reaction.

[0038] (2) Preparation of intermediate III

[0039] Add 80.5g (0.4mol) of intermediate IV prepared in the previous step to a 1000mL three-necked flask, add 500mL of tetrahydrofuran to di...

Embodiment 2

[0044] Embodiment 2 prepares 1-benzyl-3-piperidone hydrochloride

[0045] Follow the steps below:

[0046] (1) Preparation of Intermediate IV

[0047]43g (0.4mol) of benzylamine, 250mL of dichloromethane, 45.6g (0.2mol) of benzyltriethylammonium chloride, and 154.8g (1.2mol) of diisopropylethylamine were successively added to a 1000mL three-necked flask. Stir, add dropwise a solution of 217.3g (1.2mol) of ethyl bromoacetate and 150mL of dichloromethane, keep warm at 25-28°C for 4 hours after dropping, HPLC detects that the reaction is complete, and cool the reaction solution to 0-5°C Let stand for 1.5h, filter, and concentrate the filtrate under reduced pressure to obtain 75.5g (yield 97.7%) of a light brown oily substance (ie, intermediate IV), with a purity of 98.4% as detected by HPLC, which was directly put into the next reaction.

[0048] (2) Preparation of intermediate III

[0049] Add 75.5g (0.39mol) of intermediate IV prepared in the previous step to a 1000mL three-...

Embodiment 3

[0054] Embodiment 3 prepares 1-benzyl-3-piperidone hydrochloride

[0055] Follow the steps below:

[0056] (1) Preparation of Intermediate IV

[0057] 43g (0.4mol) of benzylamine, 250mL of toluene, 15g (0.057mol) of dodecyltrimethylammonium chloride, and 39.5g (0.5mol) of pyridine were successively added to a 1000mL three-necked flask. A solution of 55 g (0.45 mol) of ethyl chloroacetate and 150 mL of toluene, after dropping, keep it warm at 25-28 ° C for 4 h, after the reaction is detected by HPLC, the reaction solution is cooled to 0-5 ° C and allowed to stand for 1.5 h, filtered, and the filtrate Concentrated under reduced pressure to obtain 81.0 g (yield 105%) of a light brown oily substance (ie Intermediate IV), with a purity of 96.2% as detected by HPLC, which was directly put into the next reaction.

[0058] (2) Preparation of intermediate III

[0059] Add 81.0g (0.42mol) of intermediate IV prepared in the previous step to a 1000mL three-necked flask, add 500mL of to...

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Abstract

The invention discloses a preparation method for N-benzyl glycine ethyl ester. The method comprises the following steps: dissolving benzylamine in an organic solvent I, then adding 2-halogenated ethyl acetate, alkali and quaternary ammonium salt, and performing reaction to obtain the N-benzyl glycine ethyl ester. The invention also discloses a preparation method for 1-benzyl-3-piperidone hydrochloride. The method comprises the following specific steps: (1) preparing an intermediate IV (N-benzyl glycine ethyl ester); (2) dissolving the intermediate IV in an organic solvent II, then adding 4-halogenated ethyl acetate and alkali, and performing reaction to obtain an intermediate III; (3) performing reaction between the intermediate III and the alkali, reversely regulating a pH value to 6-8, performing concentration under reduced pressure, extracting by using ethyl acetate, performing washing and drying, and then performing concentration under reduced pressure to obtain an intermediate II; (4) performing reaction on the intermediate II and acid, performing rotary evaporation concentration, and adding a crystal solvent for crystallization to obtain a product. The route synthesis steps are short, the process is novel, the intermediates are high in purity, the product yield is high, and the cost is low.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 1-benzyl-3-piperidone hydrochloride. Background technique [0002] Halofuginone (Halofuginone, WR237645), also known as bromochlorohemosanone, haloquinone, lufuginone, is a kind of quinazolinone alkaloid febrifugine isolated from the plant Dichroa febrifuga. Halogenated derivatives. Changshanone has strong insecticidal activity, and has a strong inhibitory effect on various chicken coccidia. It is now produced by the German Hearst Company, and the trade name is "Sudan" ( ). The chemical structural formulas of hemosanone and hemosinine are as follows: [0003] [0004] 1-benzyl-3-piperidone hydrochloride is an important chemical intermediate, which can be used as the starting material for the preparation of halofloxacin and antibacterial drugs Balofloxacin and antibacterial Synthesis of leukemia drug Ibrutinib etc. The chemical structural formula o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C229/14
CPCC07C227/08C07D211/74C07C229/14
Inventor 李能刚邹晓川石开云龚雪周兴国
Owner CHONGQING WEIPENG PHARMA
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