蘭索拉唑中間體的工藝合成及優(yōu)化


本文為原創(chuàng)論文，花了一年時(shí)間在實(shí)驗(yàn)室潛心研究的結(jié)果。歡迎大家點(diǎn)擊查看。

摘要：蘭索拉唑是一種質(zhì)子泵抑制劑，能治療功能性消化不良，對(duì)基礎(chǔ)胃酸分泌和由組胺、五肽胃泌素、二丁基環(huán)腺酸、膽堿及食物等引起的胃酸形成與分泌有強(qiáng)力持久的抑制作用，同時(shí)對(duì)胃腸黏膜有保護(hù)作用。蘭索拉唑是新一代的抗酸藥及抗?jié)兯?。本課題主要以2, 3-二甲基-4-硝基氧化吡啶為原料，經(jīng)取代、加成和氯代反應(yīng)合成2-氯甲基-3-甲基-4-三氟乙氧基吡啶，并對(duì)其合成工藝進(jìn)行了優(yōu)化研究。在所選擇合理的反應(yīng)條件和工藝參數(shù)下制備了2-氯甲基-3-甲基-4-三氟乙氧基吡啶。最終得到的整條合成路線的總收率為36.1%。并采用氣相色譜、核磁共振等分析方法對(duì)合成產(chǎn)物的含量及結(jié)構(gòu)進(jìn)行了表征。
關(guān)鍵詞： 蘭索拉唑；合成；優(yōu)化；反應(yīng)條件
 
Study on the Synthesis of the Intermediate
Lansoprazole
Abstract: Lansoprazole is a proton pump inhibitor, to the treatment of functional dyspepsia, on the basis of gastric acid secretion and by histamine, pentagastrin, two-butyl central gland acid, choline and food caused by acid formation and secretion of a strong and lasting effect, Meanwhile on gastrointestinal mucosal protection role. Lansoprazole is a new generation of anti-secretory drugs and the anti-ulcer drug. The synthesis of 2-chloromethyl-3-methyl-4- trifluoroethoxy pyridine starting from 2, 3-dimethyl-4-nitropyridine oxidation, followed by replacement, addition and chlorination was improved. The related reaction conditions and factors such as catalysis of some catalysts etc were optimized. The total yield of 2-chloromethyl-3-methyl-4-trifluoroethoxy pyridine could be gave 36.1% in some rational technological parameters. The purities and structures of these compounds were confirmed by gas chromatography, 1H NMR.
Keywords: lansoprazole; synthesis; optimization; reaction conditions
 
目  錄
1  緒論 1
1.1  蘭索拉唑的介紹 1
1.2  擬采用的合成路線 5
2  實(shí)驗(yàn)部分 7
2.1  主要化學(xué)原料與試劑 7
2.2  儀器設(shè)備 7
2.2.1  實(shí)驗(yàn)用儀器 7
2.2.2  分析測(cè)試用儀器 8
2.3  2, 3-二甲基-4-三氟乙氧基N-氧化吡啶的制備 9
2.4  2-羥甲基-3-甲基-4-三氟乙氧基吡啶的制備                          9
2.5  2-氯甲基-3-甲基-4-三氟乙氧基吡啶的合成 10
2.6  產(chǎn)品分析測(cè)定                                                  11
2.6.1  熔點(diǎn)測(cè)定                                                    11
 2.6.2  薄層色譜分析                                                11
3  結(jié)果與討論 14
3.1  2, 3-二甲基-4-三氟乙氧基氧化吡啶制備的影響因素 14
3.1.1  催化劑用量對(duì)反應(yīng)的影響                                      14
3.1.2  溶劑的用量及回收率                                          15
3.1.3  反應(yīng)時(shí)間對(duì)反應(yīng)結(jié)果的影響                                    16
3.2  2-羥甲基-3-甲基-4-三氟乙氧基吡啶制備的影響因素                  16
3.2.1  合成所需注意的細(xì)節(jié)及反應(yīng)溫度的影響                          16
3.2.2  反應(yīng)時(shí)間對(duì)反應(yīng)結(jié)果的影響                                    17
3.2.3  氫氧化鈉的濃度對(duì)水解反應(yīng)的影響                              17
3.3  2-氯甲基-3-甲基-4-三氟乙氧基吡啶合成影響因素                    18
3.3.1  溫度對(duì)反應(yīng)的影響及注意事項(xiàng)                                  18
3.4  核磁共振1H NMR譜表征分析                                      19
3.4.1  2, 3-二甲基-4-三氟乙氧基氧化吡啶的表征分析                    19
3.4.2  2-羥甲基-3-甲基-4-三氟乙氧基吡啶的表征分析                    20
3.4.3  2-氯甲基-3-甲基-4-三氟乙氧基吡啶的表征分析                    21
3.5  紅外光譜IR表征                                                 22
3.5.1  2, 3-二甲基-4-三氟乙氧基氧化吡啶的紅外光譜表征                22
3.5.2  2-羥甲基-3-甲基-4-三氟乙氧基吡啶的紅外光譜表征                22
3.5.3  2-氯甲基-3-甲基-4-三氟乙氧基吡啶的紅外光譜表征               23
3.6  熔點(diǎn)測(cè)定結(jié)果                                                  23
4  結(jié)論 24
 致謝 25
參考文獻(xiàn) 26