CN105439973A - 一种手性2-羰基噁唑啉的合成方法 - Google Patents

一种手性2-羰基噁唑啉的合成方法 Download PDF

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CN105439973A
CN105439973A CN201610015714.9A CN201610015714A CN105439973A CN 105439973 A CN105439973 A CN 105439973A CN 201610015714 A CN201610015714 A CN 201610015714A CN 105439973 A CN105439973 A CN 105439973A
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carbonyl
oxazoline
chiral
oxazolin
synthesizing method
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罗梅
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Hefei Xiangchen Chemical Engineering Co Ltd
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Hefei Xiangchen Chemical Engineering Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Abstract

一种有如下结构的手性2-羰基噁唑啉：

Description

一种手性2-羰基噁唑啉的合成方法
一、技术领域
本发明涉及一种化合物的制备方法及用途，特别涉及一种手性化合物的制备方法及用途，确切地说是一种手性2-羰基噁唑啉的合成方法及用途。
二、背景技术
手性2-羰基噁唑啉是重要的医药中间体，可用来合成抗癌药物等,是国内外研究的热点之一，其合成方法有多种【1-6】。
参考文献：
1.Interactionofsubstrateandcatalystduringtheformationofoxazolidinonesfrom2-aminoalcoholsanddiethylcarbonateusingrecyclable1,3-dichlorodistannoxanes,Pulla,Sharonetal,JournalofMolecularCatalysisA:Chemical,338(1-2),33-43;2011.
2.EfficientasymmetricsynthesisofthefunctionalizedpyroglutamatecoreunitcommontooxazolomycinandneooxazolomycinusingMichaelreactionofnucleophilicglycineSchiffbasewithα,β-disubstitutedacrylate,Yamada,Takeshietal,Tetrahedron:Asymmetry,19(24),2789-2795;2008
3.Parallelkineticresolutionofactiveestersusingdesigneroxazolidin-2-onesderivedfromphenylglycineChavda,Sameeretal,Tetrahedron:Asymmetry,19(13),1536-1548;2008
4.StereoselectiveSynthesisofQuaternaryCenterBearingAzetinesandTheirβ-AminoAcidDerivativesMacNevin,ChristopherJ.etal,JournalofOrganicChemistry,73(4),1264-1269;2008.
5.KineticResolutionof2-OxazolidinonesviaCatalytic,EnantioselectiveN-Acylation,Birman,VladimirB.etal,JournaloftheAmericanChemicalSociety,128(20),6536-6537;2006.
6.ParallelkineticresolutionofD-labelled2-aryl-propionicandbutanoicacidsusingquasi-enantiomericcombinationsofoxazolidin-2-ones,Coulbeck,Elliotetal,Chirality,22(2),193-205;2010。
申请人以2-肟氰乙酸乙酯与D-苯甘氨醇为原料在142.2mol%氯化锌作催化剂下，得到了一种手性化合物(R)-4-苯基噁唑啉基-2-酮。
三、发明内容
本发明旨在提供手性化合物(R)-4-苯基噁唑啉基-2-酮。所要解决的技术问题是一步合成得到目标产物。
一种手性化合物的制备是由2-肟氰乙酸乙酯与D-苯甘氨醇在142.2mol%氯化锌作催化剂制备的由以下化学式所示的化合物：
（Ⅰ）
化学名称：(R)-4-苯基噁唑啉基-2-酮,简称化合物(I)。
本合成方法包括合成和分离，所述的合成用142.2mol%氯化锌做催化剂，2-肟氰乙酸乙酯22.3mmol，D-苯甘氨醇10.0g，用50mL氯苯做溶剂，回流反应60小时后，柱层析分离，用石油醚/二氯甲烷按体积比1：1洗脱，将收集的第一组分点自然挥发，得单晶(R)-4-苯基噁唑啉基-2-酮。
合成反应如下：
本合成方法一步得到目标产物，工艺简单，操作方便。
其反应机理可推测如下：
2-肟氰乙酸乙酯由于在空气及大量路易斯酸催化剂作用下不稳定，C=O及C=N在相邻的位置，极不稳定，反应中产生了甲酸分子或甲酸乙酯分子碎片，然后与大大过量的D-苯甘氨醇在氯化锌作用下进行缩合反应，甲酸中的羟基或甲酸乙酯中的乙氧基与D-苯甘氨醇中的氨基，及羟基分别脱去水分子或乙醇分子，得手性化合物(R)-4-苯基噁唑啉基-2-酮。
四、附图说明
图1是(R)-4-苯基噁唑啉基-2-酮的X-衍射分析图。
五、具体实施方式
在100mL两口瓶中,加入无水ZnCl24.3145g(31.7mmol),50mL氯苯,2-肟氰乙酸乙酯3.1702g(22.3mmol),D-苯甘氨醇10.0g,用50mL氯苯做溶剂，回流反应60小时后，柱层析分离，用石油醚/二氯甲烷按体积比1：1洗脱，将收集的第一组分点自然挥发，得单晶(R)-4-苯基噁唑啉基-2-酮；产率75%;[a]5 D=-30.98o(c=0.0382,CH2Cl2)：1HNMR(500MHz,CDCl3,27℃),δ(ppm)=7.34～7.45(m,5H),5.42(s,1H),4.99(t,J=0.5Hz,1H),4.78(t,J=0.5Hz,1H),4.23(t,J=0.5Hz,1H),13CNMR(125MHz,CDCl3,27℃)159.2,139.1,128.8,128.5,125.7,72.2,56.0;IR(KBr):3064,3032,2956,2924,2853,1755,1646,1603,1495,1457,1398,1360,1308,1283,1235,1077,1040,960,936,924,763,700,551,492;HRMS:m/z(%):C9H9NO2,calcdforC9H9NO2163.0633;found:163.0638。

Claims (1)

1.一种有如下结构的手性2-羰基噁唑啉：
该手性2-羰基噁唑啉的合成方法，用142.2mol%氯化锌做催化剂，2-肟氰乙酸乙酯22.3mmol，D-苯甘氨醇10.0g，用50mL氯苯做溶剂，回流反应60小时后，柱层析分离，用石油醚/二氯甲烷按体积比1：1洗脱，将收集的第一组分点自然挥发，得单晶(R)-4-苯基噁唑啉基-2-酮。
CN201610015714.9A 2016-01-12 2016-01-12 一种手性2-羰基噁唑啉的合成方法 Pending CN105439973A (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110272396A (zh) * 2019-07-23 2019-09-24 合肥祥晨化工有限公司 一种手性2-羰基噁唑啉的合成方法及用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HEIKO WERNER等: "Improved Synthesis of Aza-bis(oxazoline) Ligands", 《J.ORG.CHEM.》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110272396A (zh) * 2019-07-23 2019-09-24 合肥祥晨化工有限公司 一种手性2-羰基噁唑啉的合成方法及用途

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