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Mechanochemical Synthesis of Rosuvastatin Intermediates by Liquid-Assisted Wittig Reaction

DOI: 10.4236/oalib.1106421, PP. 1-7

Subject Areas: Chemical Engineering & Technology

Keywords: Wittig Reaction, Synthesis, Rosuvastatin Intermediates

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Liquid-assisted Wittig reaction is used to synthesis of Rosuvastatin intermediates (1,3-Dioxane-4-acetic acid, (4R,6S)-6-[(1E)-2-[4-(4-fluorophenyl)-6- (1-methylethyl)-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]ethenyl]-2,2-dimethyl-1,1-dimethylethyl ester). Evaluate the reaction using common green chemistry metrics: environmental factor (E-factor), and systematic investigation of the reaction has been made in order to study the various factors affecting the reaction. The E-factor of Liquid-assisted Wittig reaction is about a quarter of the traditional method. Under optimal conditions, the conversion rate can reach 99.2 and the E:Z ratio can reach 76:24.

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Yan, J. and Jiang, C. (2020). Mechanochemical Synthesis of Rosuvastatin Intermediates by Liquid-Assisted Wittig Reaction. Open Access Library Journal, 7, e6421. doi:


[1]  Byrnea, P.A. and Gilheany, D.G. (2013) The Modern Interpretation of the Wittig Reaction Mechanism. Chemical Society Reviews, 42, 6670.
[2]  Hoffmann, M., Deshmukh, S. and Werner, T. (2015) Scope and Limitation of the Microwave-Assisted Catalytic Wittig Reaction. European Journal of Organic Chemistry, 20, 4532-4543.
[3]  Davidson, M.H. and Robinson, J.G. (2006) Lipid-Lowering Effects of Statins: A Comparative Review. Expert Opinion on Pharmacotherapy, 7, 1701-1714.
[4]  Dogan, S., Duivenvoorden, R., Grobbee, D.E., et al. (2010) Ultrasound Protocols to Measure Carotid Intima-Media Thickness in Trials; Comparison of Reproducibility, Rate of Progression, and Effect of Intervention in Subjects with Familial Hypercholesterolemia and Subjects with Mixed Dyslipidemia. Annals of Medicine, 42, 447-464.
[5]  Casar, Z., Steinbücher, M. and Kosmrlj, J. (2010) Lactone Pathway to Statins Utilizing the Wittig Reaction. The Synthesis of Rosuvastatin. Journal of Organic Chemistry, 75, 6681-6684.
[6]  Deshpande, P.B. (2009) Process for Preparation of Rosuvastatin, U.S. Patent 20090124803A1.
[7]  Joshi, N., Bhirud, S.B. and Chandrasekhar, B. (2005) An Improved Process for Preparation of Rosuvastatin Derivatives, Useful as HMG-CoA Inhibitor. U.S. Patent 20050124639.
[8]  Vempala, N., Rao, S. V., Shree, A.J. and Pradhan, B.S. (2016) An Asymmetric Synthesis of Rosuvastatin Calcium. Synthesis, 48, 4167-4174.
[9]  Xiong, F.J., Wang, H.F., Yan, L.J., Han, S., Tao, Y., Wu, Y. and Chen, F.E. (2016) Stereocontrolled Synthesis of Rosuvastatin Calcium via Iodine Chloride-Induced Intramolecular Cyclization. Organic & Biomolecular Chemistry, 14, 1363-1369.
[10]  Gudipati, S., Katkam, S., Sagyam, R.R. and Kudavalli, J.S. (2007) Processes to Produce Intermediates for Rosuvastatin. U.S. Patent 7161004B2.
[11]  Uchiyama, Y., Ohtsuki, T., Murakami, R., Shibata, M. and Sugimoto, J. (2017) (E)-Selective Wittig Reactions between a Nonstabilized Phosphonium Ylide Bearing a Phosphastibatriptycene Skeleton and Benzaldehydes. European Journal of Organic Chemistry, 2017, 159-174.
[12]  Valkute, T.R., Aratikatla, E.K. and Bhattacharya, A.K. (2017) Efficient Synthesis of Functionalized Olefins by Wittig Reaction Using Amberlite Resin as a Mild Base. Synthetic Communications, 47, 581-589.
[13]  Schirmer, M.-L., Adomeit, S. and Werner, T. (2015) First Base-Free Catalytic Wittig Reaction. Organic Letters, 17, 3078-3081.
[14]  Okuma, K., Sakai, O. and Shioji, K.B. (2003) Wittig Reaction by Using DBU as a Base. Bulletin of the Chemical Society of Japan, 76, 1675-1676.
[15]  Westman, G., Wennerstr?m, O. and Raston, I. (1993) On the Effect of Cyclodextrin on the Z/E-Selectivity of Wittig Reactions with Semistabilized Ylides. Tetrahedron, 49, 483-488.
[16]  Ward Jr., W.J. and McEwen, W.E. (1990) Metal Ion Effects in Wittig Reactions. A General Hypothesis for the Mechanism of the Wittig Reaction. The Journal of Organic Chemistry, 55, 493-500.
[17]  Balema, V.P., Wiench, J.W., Pruski, M. and Pecharsky, V.K. (2002) Mechanically Induced Solid-State Generation of Phosphorus Ylides and the Solvent-Free Wittig Reaction. Journal of the American Chemical Society, 124, 6244-6245.
[18]  Ribeiro, M.G.T.C., Costa, D.A. and Machado, A.A.S.C. (2010) “Green Star”: A Holistic Green Chemistry Metric for Evaluation of Teaching Laboratory Experiments. Green Chemistry Letters and Reviews, 3, 149-159.


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