论文总字数：15566字

摘 要

镇痛药会选择性的抑制和缓解人身体的各种疼痛，它是为了减轻我们人类精神上和生理上的病痛，镇痛药主要作用的是我们的中枢神经系统。镇痛的同时不会影响人的身体机能，并保持意识的清醒。但有些镇痛药重复的使用会导致人体成瘾及产生依赖效果。凡是容易使人上瘾的药品，研究人员称为“麻醉性镇痛药”，被药政管理列为“麻醉药品”，为了保障人类身体健康，我们国家颁布了相关法律，明令禁止随便使用镇痛药物，并对生产和临床治疗都严格的限制和管控。

盐酸他喷他多，化学名为3-[(1R,2R)-3-（二甲氨基）-1-乙基-2-甲基丙基]苯酚盐酸盐，是由美国Johnsonamp;Johnson公司研制开发的药物，2008年11月首次在美国上市。其为一种有效的口服中枢镇痛药，具有两种作用机制：一种是作用于人类μ受体，通过改善情感因素和人类身体疼痛感觉，使疼痛在脊髓中的传递得到抑制作用，从而控制和影响我们痛感在大脑皮层部位的活动，另一种机制是对去肾上腺素重摄取的抑制，主要是通过抑制去甲肾上腺素再吸收进入神经细胞，进而使大脑中的去肾上腺素浓度上升这样便能起到镇痛的作用^[1]。因为盐酸他喷他多的作用机制不是依靠代谢活化作用，而且也没有代谢活化产生的物质，对各种神经痛和急性炎症均具有较好的作用，其效能介于曲马多和吗啡之间，与其他镇痛类药物相比，不良反应较轻且耐受性良好^[2]。

合成盐酸他喷他多的重要中间体中就包含了3-（二甲氨基）-1-（3-苄氧苯基）-2-甲基-1-丙酮盐酸盐。我的论文研究课题就是根据合成3-（二甲氨基）-1-（3-苄氧苯基）-2-甲基-1-丙酮盐酸盐的工艺路线而展开的。

选择工艺路线，原料及投料量的选择、操作过程中溶剂的选择以及质量控制都是重要的因素。

综合考虑产物的纯度、合成困难、成本以及环保等因素的困难选择曼尼希反应用SMA、二甲胺盐酸盐、多聚甲醛作为原料。

关键词：镇痛药，他喷他多，丙酮盐酸盐，μ受体，工艺路线，曼尼希反应，SMA

Abstract

Analgesics a major role in the central nervous system, the selective inhibition of the human body and relieve all kinds of pain, the purpose is to reduce the pain caused by physical and mental suffering, pain at the same time does not affect the function of the human body, and stay awake consciousness.But some analgesics repeated use can lead to addiction and dependence of human effects. All addictive drugs, generally known as "narcotic analgesics" by the Pharmaceutical Affairs as "Narcotic Drugs", in order to protect human health, the state promulgated the "Regulations on Narcotic Drugs", the production and use of both supply It is strictly regulated and limited.

Tapentadol hydrochloride, the chemical name 3 - [(1R, 2R) -3- (dimethylamino) -1-ethyl-2-methylpropyl] phenol hydrochloride, by the United States Johnson amp; Johnson company developed drugs, in November 2008 for the first time in the United States. Its analgesic as an effective oral center,It has two mechanisms: one is the role of the human μ receptor, emotional factors and by improving the human body sensation of pain, so pain in the spinal cord passes obtained inhibition to control pain and impact of our activities in parts of the cerebral cortex, another mechanism is a norepinephrine reuptake inhibition, by inhibiting norepinephrine reuptake into the nerve cells to increase the concentration of norepinephrine in the brain and thus play analgesic effect.Because tapentadol hydrochloride is not dependent metabolic activation and without metabolic activation products for a variety of neuropathic pain and acute inflammation have a good effect, its effectiveness is between tramadol and morphine, and other analgesics compared to drugs, adverse effects were mild and well tolerated.

3- (dimethylamino) -1- (3-benzyloxy-phenyl) -2-methyl-1-propanone hydrochloride as synthetic tapentadol hydrochloride important intermediates. This paper is to study the 3- (dimethylamino) -1- (3-benzyloxyphenyl) -2-methyl-1-propanone routing hydrochloride.

Route selection process, raw materials and feeding amount of choice, the choice of solvent during the operation and quality control are important factors.

Considering the difficulties of product purity, synthetic difficulty, cost and environmental factors such as the choice of the SMA Mancini reaction, dimethylamine hydrochloride, paraformaldehyde as a raw material.

Keywords: analgesic tapentadol, acetone, hydrochloride, μ receptor, routing, Mancini reaction, SMA

目 录

摘　要 3

Abstract 4

第一章 文献综述 6

1.盐酸他喷他多 8

1.1药品名称 8

1.2化学结构式： 8

1.3物理性状： 8

1.4适应症： 8

1.5作用机制： 8

1.6工艺路线 9

第二章 3-（二甲氨基）-1-（3-苄氧苯基）-2-甲基-1-丙酮盐酸盐的合成工艺研究 13

2.1关键起始物料制备工艺 13

2.2中间体1的合成方法 14

2.3中间体1的工艺优化 15

2.5中间体1生产工艺的溶剂测试 17

第三章 展望 18

参考文献 20

附　录 21

剩余内容已隐藏，请支付后下载全文，论文总字数：15566字