(S)-1-苄基吡咯烷-3-醇的合成新方法
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摘要
以廉价易得的反式L-羟基脯氨酸为原料,经脱羧、苄基化、甲磺酰化、构型翻转及水解等5步反应得到标题化合物,总收率41.72%,手性纯度>99%。目标产物经高分辨质谱、核磁氢谱等确证。整条路线收率高、成本低且操作简便,适用于放大生产。
Using cheap and easily achieved L-hydroxyproline as starting material,the important medicinal intermediate( S)-1-benzylpyrrolidin-3-ol was prepared via decarboxylation,benzylation,mesylation,configuration reversed and hydrolyzation with a total yield of 41. 72% and chiral purity of more than 99%. The compound was confirmed by HR-MS,~1HNMR. This protocol featured by high yield,low cost and easy to operate,and thus suitable for its scale up preparation.
Using cheap and easily achieved L-hydroxyproline as starting material,the important medicinal intermediate( S)-1-benzylpyrrolidin-3-ol was prepared via decarboxylation,benzylation,mesylation,configuration reversed and hydrolyzation with a total yield of 41. 72% and chiral purity of more than 99%. The compound was confirmed by HR-MS,~1HNMR. This protocol featured by high yield,low cost and easy to operate,and thus suitable for its scale up preparation.
引文
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[3]廖云凤,翁志洁,李建其.3-(S)-(-)-(1-氨甲酰基-1,1-二苯甲基)吡咯烷酒石酸盐的制备[J].中国医药工业杂志,2011,42(5):323-325.
[4]ZHENG Jin-li,LIU Hui,ZHANG Yu-feng,et al.A study on the racemization step in the synthesis of pyrrolidinols via cyclicα-hydroxyimides[J].Tetrahedron:Asymmetry,2011,22(3):257-263.
[5]AGA M A,KUMAR B,ROUF A,et al.Natural(-)-vasicine as a novel source of optically pure 1-benzylpyrrolidin-3-ol[J].Helv.Chim.Acta,2013,96(5):969-977.
[6]CHEN Yong-zheng,TANG Weng-lin,MOU Jie,et al.High-throughput method for determining the enantioselectivity of enzyme-catalyzed hydroxylations based on mass spectrometry[J].Angew.Chem.Int.Ed.,2010,49(31):5 278-5 283.
[7]PHAM S Q,POMPIDER G,LIU Ji,et al.Evolving P450pyr hydroxylase for highly enantioselective hydroxylation at non-activated carbon atom[J].Chem.Commun.,2012,48(38):4 618-4 620.
[8]CHRISTOPH G,STRATMANN C,COLDHAM I,et al.Asymmetric synthesis of 3-hydroxy-pyrrolidines via tinlithium exchange and cyclization[J].Org.Lett.,2006,8(20):4 469-4 471.
[9]MORIMOTO M,SAKAI K.Practical synthetic process for enantiopure 1-benzyl-3-hydroxypyrrolidine[J].Tetrahedron:Asymmetry,2008,19(12):1 465-1 469.
[10]TOFANI G,PETRI A,PICCOLO O.Preparation of enantiomerically pure N-heterocyclic amino alcohols by enzymatic kinetic resolution[J].Tetrahedron:Asymmetry,2015,26(12/13):638-643.
[11]HORIGUCHI A,MOCHIDA K I.Enzymatic optical resolution of N-benzyl-3-pyrrolidinol[J].Biosci.Biotechol.Biochem.,1995,59(7):1 287-1 290.
[12]刘长欢,俞雄,袁哲东.氢溴酸达非那新的合成[J].中国医药工业杂志,2007,38(12):825-827.
[13]HUANG Yun-sheng,LUEDKE R R,FREEMAN R A,et al.Synthesis and structure-activity relationships of naphthamides as dopamine D3 receptor ligands[J].J.Med.Chem.,2001,44(11):1 815-1 826.