A Practical and Efficient Synthesis of (±)-Rivastigmine

Abstract

A practical and efficient synthesis of (±)-rivastigmine, which is an acetyl cholinesterase inhibitor of the carbamate family and has been approved for the treatment of Alzheimer's disease in more than 60 countries, was developed in three steps from cheap and commercially available 3-ethylphenol. The key step of the synthesis involved the NBS-promoted benzylic bromination of 3-ethylphenyl ethyl(methyl)carbamate. The target molecular was obtained in 71% overall yield without any traditional purification (column chromatography or crystallization). The reactions include esterification, benzylic bromination, substitution reaction.

A Practical and Efficient Stereoselective Synthesis of (S)‐Rivastigmine and (R)‐Rivastigmine

“…In connection with our previous synthetic work on natural products using halogenation as a key step, we completed the synthesis of (±)‐rivastigmine . In this context, the purpose was to find an efficient method for stereoselective synthesis of rivastigmine.…”

“…In connection with our previous synthetic work on natural products using halogenation as a key step, [34][35][36] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 the synthesis of (AE)-rivastigmine. [37] In this context, the purpose was to find an efficient method for stereoselective synthesis of rivastigmine. Surprisingly, during the mesylation of alcohol 2 (Scheme 2) to 4, [25] chloride 5 was obtained directly instead of the expected sulfonate 4.…”

Probing nuclear symmetry energy at high densities using pion, kaon, eta and photon productions in heavy-ion collisions

“…The central components of CEE are the tracking detectors inside and downstream to a dipole with large acceptance at forward and midrapidity in laboratory reference. For the forward rapidity acceptance, it is expected to provide complementary data to the existing devices [90]. Meanwhile, further observables , for instance, the balance energy of direct nucleon flow [91], the scattering angles of the nucleons on a heavy target [92], are demonstrated sensitively probing the symmetry energy at high densities.…”

Synthesis and Antimicrobial Activities of Novel 1,2,4-Triazole-acyl-hydrazone Derivatives Containing the Quinazolin-4-one Moiety

“…另一方面, 喹唑啉-4-酮是一类广谱的药 效基团, 具有多种优良生物活性, 如抗细菌 [15] 、抗真 菌 [16] 、抗肿瘤 [17] 和抗病毒 [18] 等, 已商品化的喹唑啉酮类 杀 菌 剂 有 氟 喹 唑 ( F l u q u i n c o n a z o l e ) 和 阿 巴 康 唑 (Albaconazole). 以往的研究表明在同一分子中引入结 构不同的抗菌活性片段, 有可能筛选出抗菌活性更高、 抗菌谱更广的化合物 [19,20] . 基于以上原因并结合本课题 [24] : 214～215 ℃)和 98～101 ℃(文献值 [26] : 103～105 ℃).…”