CN111170929A - 一种由末端烯烃制备β-氨基醇的方法 - Google Patents

一种由末端烯烃制备β-氨基醇的方法 Download PDF

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CN111170929A
CN111170929A CN201911270981.0A CN201911270981A CN111170929A CN 111170929 A CN111170929 A CN 111170929A CN 201911270981 A CN201911270981 A CN 201911270981A CN 111170929 A CN111170929 A CN 111170929A
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颜世强
郭伟
何淑旺
王文笙
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Shandong Dyne Marine Biotechnological Pharm Holdings Co ltd
Beijing Dayin High Tech Children Medicine Research Institute Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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    • C07—ORGANIC CHEMISTRY
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    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Abstract

本发明提供一种由末端烯烃制备β‑氨基醇的方法。该方法以末端烯烃为原料，首先加入二溴海因搅拌，然后再加入有机胺，得到相应的β‑氨基醇。本发明的方法条件温和、易于操作，所用原料廉价，具有广泛的应用前景。

Description

一种由末端烯烃制备β-氨基醇的方法
技术领域
本发明属于精细化工产品的制备、药物中间体的合成领域，具体涉及利用末端烯烃制备β-氨基醇的一种新方法。
背景技术
β-氨基醇是药物化学和天然产物中的重要结构片段。在很多已上市的药物和生物活性分子，例如拟肾上腺素药麻黄碱，β1肾上腺素能受体阻滞剂美托洛尔以及短效β2肾上腺素能受体激动剂沙丁胺醇、妥洛特罗等均存在该结构。之前报道该结构片段合成方法多集中于使用重金属试剂，如Sharpless等报道在锇催化作用下由烯烃不对称合成邻二醇和β-氨基醇 (Andersson,M.A.et Al.Angew.Chem.Int.Edit.2002,41(3),472-475)；Hergenrother和Muniz 在Sharpless的工作基础上，通过调整pH值和锇试剂等条件，提高了产物中β-氨基醇的比例 (Muniz,K.,Eur.J.Org.Chem.2004,(10),2243-2252；Nesterenko,V.et Al.Org.let.2003,5(3), 281-284)；2016年，Morandi报道了使用Fe(II)复合物催化合成β-氨基醇的方法(Legnani,L.et Al.Angew.Chem.Int.Edit.2016,55(6),2248-2251)。以上均使用了金属催化剂，有潜在的环境污染隐患。其他亦有通过α-氨基酮还原、次苄基溴在DMSO中一锅合成的方法，但并未进行***研究(Song,S.et Al.Green Chem.2015,17(5),2727-2731；Prasad,P.K.et Al.Org.lett. 2016,18(3),500-3)。
Figure BDA0002314126050000011
发明内容
本发明提供的方法，可以十分有效的将芳香环取代的末端烯烃转化为β-氨基醇。相比已有报道，该方法原料易得、成本低廉，所用试剂毒性较小，且具有更高收率和纯度，更好的底物兼容性，更广泛的用途、较大的成本和环保优势。
本发明的目的是这样实现的：将末端烯烃溶于溶剂，首先加入二溴海因搅拌一段时间，然后再加有机胺，得到相应的β-氨基醇。
所用的末端烯烃，可以是由芳环或脂肪环构成的末端烯烃；所用的有机胺，可以是由脂肪链或脂肪环构成的有机胺。
本发明提供一种制备β-氨基醇的方法，以烯烃1为原料，首先加入二溴海因，然后再加入有机胺R2R3NH，得到相应的β-氨基醇2；
Figure BDA0002314126050000021
其中，R选自C1-C20烷基、取代基取代或未取代的C5-C20芳基，或上述R任选的可与烯基成取代基取代或未取代的环，所述取代基选自C1-C20烷基、卤素、硝基、羟基、C1-C20烷氧基、C1-C20烷氧基C1-C20烷基、羟基C1-C20烷基；
R2和R3各自独立地选自H、C1-C20烷基，或R2和R3可与N形成取代基取代或未取代的5-6元饱和杂环，所述取代基选自C1-C20烷基。
本发明所述C1-C20烷基是指具有1-20个碳原子的直链或支链烷基，例如C1-C6烷基，例如可为甲基、乙基、正丙基、异丙基、正丁基、仲丁基、异丁基、叔丁基、正戊基、异戊基或正己基等。
本发明所述C5-C20芳基是指具有5-20个碳原子的芳基，例如C5-C10烷基，例如可为苯基、萘基等。
本发明所述卤素为卤族元素，例如可为F、Cl、Br或I。
上述制备β-氨基醇的方法，其中，R选自C1-C6烷基、取代基取代或未取代的苯基，所述取代基取代位置为苯基的1-、2-和/或3-位；或R与烯基形成取代基取代或未取代的四氢萘或茚；所述取代基选自C1-C6烷基、卤素、硝基。
上述制备β-氨基醇的方法，其中，R2和R3各自独立地选自H、C1-C6烷基，或R2和 R3可与N形成取代基取代或未取代的5-6元饱和杂环，所述取代基选自C1-C6烷基。
上述制备β-氨基醇的方法，其中，R2和R3各自独立地选自H、甲基、乙基、丙基、叔丁基，或R2R3NH为4-甲基哌啶或哌啶。
上述制备β-氨基醇的方法，反应路线如下，
Figure BDA0002314126050000031
其中，R1选自C1-C20烷基、卤素、硝基、羟基、C1-C20烷氧基、C1-C20烷氧基C1-C20烷基、羟基C1-C20烷基，R1取代位置为苯基的1-、2-和/或3-位；或R1与烯基苯基形成取代基取代或未取代的四氢萘或茚；所述取代基选自C1-C20烷基、卤素、硝基、羟基、C1-C20烷氧基、C1-C20烷氧基C1-C20烷基、羟基C1-C20烷基；
R2和R3各自独立地选自H、C1-C20烷基，或R2和R3可与N形成取代基取代或未取代的5-6元饱和杂环，所述取代基选自C1-C20烷基。
上述制备β-氨基醇的方法，R1选自C1-C6烷基、卤素、硝基；R2和R3各自独立地选自H、C1-C6烷基，或R2和R3可与N形成取代基取代或未取代的5-6元饱和杂环，所述取代基选自 C1-C6烷基。
上述制备β-氨基醇的方法，R2和R3各自独立地选自H、甲基、乙基、丙基、叔丁基，或R2R3NH为4-甲基哌啶或哌啶。
上述制备β-氨基醇的方法，其中，β-氨基醇2选自如下化合物：
Figure BDA0002314126050000041
本发明上述制备β-氨基醇的方法，所用的反应溶剂体系为丙酮--水、乙腈--水、1,4-二氧六环--水、N,N-二甲基甲酰胺--水中的一种或它们的混合物，优选丙酮--水；
本发明上述制备β-氨基醇的方法，所用的反应溶剂体系丙酮--水的体积比优选1:1～20: 1，更优选4:1～6:1，进一步优选5:1；
本发明上述制备β-氨基醇的方法，末端烯烃与二溴海因的摩尔比优选1:0.1～1:1，更优选1:0.4～1:0.6，进一步优选1:0.55；
本发明上述制备β-氨基醇的方法，有机胺与末端烯烃的摩尔比优选1:1～10:1，更优选 2:1～5:1，进一步优选3:1；
本发明上述制备β-氨基醇的方法，反应时间为0.5～48小时，进一步优选2～4小时。
具体实施方式
以下为本发明的具体实施例，但本发明不仅仅局限于以下实施例。
制备通法：取烯烃5.0mmol加入到含丙酮15mL以及水3mL的混合反应体系中，在搅拌条件下加入二溴海因2.75mmol，然后室温搅拌，待反应完全后，向其中加入15.0mmol的有机胺并在室温下继续搅拌4h。反应结束后向反应液中加入20mL饱和亚硫酸钠溶液，然后以乙酸乙酯萃取三次，分出有机层，减压浓缩除去有机溶剂，通过柱层析或重结晶分离，得到产物。代表性的反应原料、对应的产物结构和收率如下所示：
Figure BDA0002314126050000051
实施例1：以苯乙烯及4-甲基哌啶为原料，按通法制备，收率84％。产物2a的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.35(dt,J＝15.0,7.5Hz,4H),7.26(t,J＝7.1Hz,1H),4.71(dd,J＝10.5,3.6Hz,1H),4.21(s,1H),3.12(d,J＝11.4Hz,1H),2.76(d,J＝11.6Hz, 1H),2.54–2.37(m,2H),2.29(td,J＝11.5,2.3Hz,1H),2.00(td,J＝11.6,2.3Hz,1H),1.71–1.56 (m,2H),1.44–1.17(m,3H),0.94(d,J＝6.4Hz,3H)；13C NMR(125MHz,CDCl3)δ142.50, 128.29,127.36,125.85,68.77,66.56,55.59,52.14,34.68,34.31,30.73,21.89.
实施例2：以4-甲基苯乙烯及4-甲基哌啶为原料，按通法制备，收率75％。产物2b的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.25(d,J＝4.1Hz,2H),7.15(d,J＝7.9Hz,2H),4.68(dd,J＝10.3,3.8Hz,1H),4.18(s,1H),3.11(d,J＝11.8Hz,1H),2.76(d,J＝11.8Hz, 1H),2.43(qd,J＝12.5,7.2Hz,2H),2.33(s,3H),2.28(td,J＝11.5,2.5Hz,1H),1.99(td,J＝11.6, 2.5Hz,1H),1.70–1.58(m,2H),1.45–1.35(m,1H),1.26(dddd,J＝24.5,15.7,11.8,4.0Hz,2H), 0.94(d,J＝6.4Hz,3H)；13C NMR(125MHz,CDCl3)δ139.48,136.99,129.01,125.84,68.65, 66.63,55.63,52.14,34.72,34.35,30.77,21.91,21.15.
实施例3：以3-甲基苯乙烯及4-甲基哌啶为原料，按通法制备，收率64％。产物2c的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.29–7.12(m,4H),4.74(dd,J＝8.9,4.6Hz, 1H),3.87(s,1H),3.17(d,J＝11.5Hz,1H),2.85(d,J＝11.8Hz,1H),2.54–2.43(m,2H),2.35– 2.31(t,J＝10.4Hz,4H),2.12–2.01(m,1H),1.66(t,J＝13.2Hz,2H),1.42–1.24(m,3H),0.95 (d,J＝6.2Hz,3H)；13C NMR(125MHz,CDCl3)δ139.24,137.11,129.05,128.23,126.52,125.84, 122.98,68.66(d,J＝17.8Hz),66.44,55.56,52.27,34.36,34.03,30.61,21.81,21.14.
实施例4：以4-叔丁基苯乙烯及4-甲基哌啶为原料，按通法制备，收率82％。产物2d的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.36(d,J＝8.3Hz,2H),7.30(d,J＝8.3Hz,2H),4.69(dd,J＝9.8,4.4Hz,1H),4.17(s,1H),3.13(d,J＝11.5Hz,1H),2.77(d,J＝11.6Hz, 1H),2.51–2.38(m,2H),2.29(td,J＝11.5,2.4Hz,1H),1.99(td,J＝11.6,2.4Hz,1H),1.74–1.59 (m,2H),1.49–1.16(m,3H),1.31(s,9H),0.94(d,J＝6.4Hz,3H)；13C NMR(125MHz,CDCl3)δ 150.34,139.39,125.67,125.26,68.61,66.50,55.66,52.14,34.75,34.54,34.37,31.42,30.80, 21.94.
实施例5：以4-氟苯乙烯及4-甲基哌啶为原料，按通法制备，收率88％。产物2e的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.33(dd,J＝8.5,5.5Hz,2H),7.02(t,J＝8.7Hz,2H),4.68(dd,J＝10.6,3.5Hz,1H),4.24(s,1H),3.10(d,J＝11.6Hz,1H),2.75(d,J＝11.7 Hz,1H),2.45(dd,J＝12.5,3.6Hz,1H),2.41–2.33(m,1H),2.29(td,J＝11.5,2.4Hz,1H),2.00 (td,J＝11.6,2.4Hz,1H),1.69–1.60(m,2H),1.39(tt,J＝7.0,5.3Hz,1H),1.26(dddd,J＝24.5, 15.8,11.9,4.0Hz,2H),0.94(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3)δ163.13,161.19, 138.20(d,J＝3.0Hz),127.47(d,J＝8.0Hz),115.20,115.03,68.22,66.57,55.61,52.14,34.68, 34.31,30.72,21.88.
实施例6：以3-氯苯乙烯及4-甲基哌啶为原料，按通法制备，收率78％。产物2f的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.39(s,1H),7.28–7.20(m,3H),4.67(dd,J＝10.7,3.5Hz,1H),4.26(s,1H),3.12–3.04(m,1H),2.81–2.69(m,1H),2.48(dd,J＝12.4,3.6Hz, 1H),2.40–2.25(m,2H),2.01(td,J＝11.6,2.5Hz,1H),1.73–1.57(m,2H),1.44–1.35(m,1H), 1.26(dddd,J＝24.6,15.8,11.8,4.0Hz,2H),0.94(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3) δ144.77,134.25,129.55,127.44,125.99,123.96,68.20,66.30,55.55,52.11,34.64,34.27,30.68, 21.86.
实施例7：以4-氯苯乙烯及4-甲基哌啶为原料，按通法制备，收率83％。产物2g的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.30(s,4H),4.67(dd,J＝10.7,3.5Hz,1H),4.25(s,1H),3.09(d,J＝11.9Hz,1H),2.78–2.69(m,1H),2.46(dd,J＝12.4,3.5Hz,1H),2.39– 2.24(m,2H),2.00(td,J＝11.6,2.5Hz,1H),1.70–1.58(m,2H),1.50–1.35(m,1H),1.25(dddd, J＝28.5,24.5,11.9,4.0Hz,2H),0.94(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3)δ141.09, 132.94,128.44,127.21,68.17,66.40,55.58,52.13,34.66,34.29,30.69,21.87.
实施例8：以3-溴苯乙烯及4-甲基哌啶为原料，按通法制备，收率85％。产物2h的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.54(s,1H),7.38(d,J＝7.9Hz,1H),7.28(d,J ＝7.7Hz,1H),7.20(t,J＝7.8Hz,1H),4.66(dd,J＝10.7,3.5Hz,1H),4.26(s,1H),3.09(d,J＝ 11.8Hz,1H),2.74(d,J＝11.7Hz,1H),2.48(dd,J＝12.4,3.6Hz,1H),2.39–2.26(m,2H),2.01 (td,J＝11.6,2.4Hz,1H),1.71–1.60(m,2H),1.39(tt,J＝7.1,5.3Hz,1H),1.26(dddd,J＝28.4, 24.6,11.9,4.0Hz,2H),0.94(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3)δ145.03,130.38, 129.87,128.90,124.44,122.50,68.14,66.31,55.55,52.10,34.64,34.27,30.68,21.87.
实施例9：以2-氯苯乙烯及叔丁胺为原料，按通法制备，收率77％。产物2i的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.63(dd,J＝7.7,1.3Hz,1H),7.34–7.25(m,2H),7.19(td,J＝7.7,1.6Hz,1H),4.99(dd,J＝8.6,3.5Hz,1H),3.02(dd,J＝12.1,3.5Hz,1H),2.47 (dd,J＝12.0,8.6Hz,1H),1.09(s,9H)；13C NMR(125MHz,CDCl3)δ140.91,131.63,129.12, 128.18,127.46,126.91,68.78,50.42,48.12,29.00.
实施例10：以苯乙烯及叔丁胺为原料，按通法制备，收率67％。产物2j的核磁共振波谱数据如下：1H NMR(500MHz,CDCl3)δ7.45–7.25(m,5H),4.65(dd,J＝9.1,3.5Hz,1H),3.59(s,2H),2.88(dd,J＝11.9,3.5Hz,1H),2.63(dd,J＝11.8,9.1Hz,1H),1.12(s,9H)；13CNMR (125MHz,CDCl3)δ142.71,128.66,128.38,127.49,125.89,125.81,71.92,50.98,50.13,29.43, 28.77.
实施例11：以苯乙烯及二乙胺为原料，按通法制备，收率78％。产物2k的核磁共振波谱数据如下：1H NMR(400MHz,cdcl3)δ7.46–7.23(m,5H),4.64(dd,J＝10.6,3.5Hz,1H),3.74 (s,1H),2.74(dq,J＝14.5,7.3Hz,2H),2.66–2.52(m,3H),2.45(dd,J＝12.7,10.7Hz,1H),1.07 (t,J＝7.1Hz,6H)；13C NMR(CDCl3,150MHz)δ:142.67,128.31,127.36,125.84,69.23,61.84, 46.90,11.99.
实施例12：以4-氯苯乙烯及二乙胺为原料，按通法制备，收率75％。产物2l的核磁共振波谱数据如下：1H NMR(CDCl3,400MHz)δ:7.33(dd,J＝8.5,5.5Hz,1H),7.01(t,J＝8.7Hz,1H), 4.60(dd,J＝10.6,3.4Hz,0H),4.01(s,0H),2.70(dt,J＝14.4,7.2Hz,2H),2.62–2.45(m,3H), 2.38(dd,J＝12.8,10.6Hz,1H),1.06(td,J＝7.2,2.6Hz,4H)；13C NMR(CDCl3,150MHz)δ: 141.26,132.91,128.43,127.18,68.62,61.69,46.89,11.97.
实施例13：以3-溴苯乙烯及二乙胺为原料，按通法制备，收率68％。产物2m的核磁共振波谱数据如下：1H NMR(CDCl3,400MHz)δ:7.53(s,1H),7.38–7.34(m,1H),7.26(d,J＝7.7 Hz,1H),7.17(t,J＝7.8Hz,1H),4.57(dd,J＝10.5,3.6Hz,1H),4.19(s,1H),2.75–2.47(m,5H), 2.36(dd,J＝12.8,10.5Hz,1H),1.03(t,J＝7.1Hz,6H)；13C NMR(CDCl3,150MHz)δ:145.17, 130.22,129.76,128.75,124.33,122.39,68.54,61.54,46.79,11.89.
实施例14：以4-氟苯乙烯及二乙胺为原料，按通法制备，收率55％。产物2n的核磁共振波谱数据如下：1H NMR(CDCl3,400MHz)δ:7.33–7.28(m,4H),4.60(dd,J＝10.5,3.6Hz,1H),4.06(s,1H),2.77–2.65(m,2H),2.63–2.50(m,3H),2.41–2.33(m,1H),1.13–1.01(m,6H)；13C NMR(CDCl3,150MHz)δ:162.97,161.35,138.37,128.45,127.46,127.41,127.19,115.19, 115.05,68.68,61.83,46.91,11.99.
实施例15：以3-硝基苯乙烯及二乙胺为原料，按通法制备，收率66％。产物2o的核磁共振波谱数据如下：1H NMR(CDCl3,400MHz)δ:8.26(s,1H),8.15–8.06(m,1H),7.73(d,J＝7.7 Hz,1H),7.52(dd,J＝10.5,5.3Hz,1H),4.74(dd,J＝10.4,3.7Hz,1H),4.43(s,1H),2.88–2.67(m, 3H),2.60(dq,J＝13.9,7.0Hz,2H),2.40(dd,J＝12.8,10.5Hz,1H),1.07(t,J＝7.1Hz,6H)；13C NMR(CDCl3,150MHz)δ:148.15,145.07,131.82,129.07,122.07,120.61,68.31,61.28,46.73, 11.76.
实施例16：以2-苯乙烯及甲胺为原料，按通法制备，收率78％。产物2p的核磁共振波谱数据如下：1H NMR(CDCl3,400MHz)δ:7.39–7.27(m,5H),4.16–4.03(m,1H),3.54(d,J＝3.9 Hz,1H),3.16(s,1H),2.37(s,3H),1.44(s,1H),0.99(d,J＝6.4Hz,3H)；13C NMR(CDCl3,150 MHz)δ:138.34,128.43,128.34,127.70,70.01,68.71,33.07,18.77.
实施例17：以四氢萘及二乙胺为原料，按通法制备，收率46％。产物2q的核磁共振波谱数据如下：1H NMR(CDCl3,400MHz)δ:7.3–7.27(m,1H),7.18–7.07(m,3H),3.82(d,J＝9.3 Hz,1H),3.75–3.61(m,2H),2.98–2.73(m,6H),2.32–2-24(m,1H),1.88–1.76(m,1H),1.17(t,J＝ 7.2Hz,6H)；13C NMR(CDCl3,150MHz)δ:137.65,136.57,128.93,127.39,126.39,126.32,68.42, 68.40,47.16,29.44,28.22,16.60.
实施例18：以茚及二乙胺为原料，按通法制备，收率53％。产物2r的核磁共振波谱数据如下：1H NMR(CDCl3,400MHz)δ:7.27–7.16(m,1H),7.12–7.02(m,3H),4.41(dd,J＝16.3Hz, 7.2Hz,1H),4.21(d,J＝6.1Hz,1H),3.57(s,1H),3.15-3.07(m,1H),2.72–2.65(m,1H), 2.61–2.53(m,4H),1.03(t,J＝7.1Hz,6H)；13C NMR(CDCl3,150MHz)δ:141.39,140.18,127.37, 126.41,125.06,124.87,74.77,73.62,45.10,39.17,14.52.
本发明实施例的用途仅用于说明本发明而非意欲限制本发明的保护范围。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (10)

1.一种由末端烯烃制备β-氨基醇的方法，其特征在于以末端烯烃为原料，首先加入二溴海因，然后再加入有机胺，得到相应的β-氨基醇。
2.如权利要求1所述的制备β-氨基醇的方法，所述的末端烯烃，可以是由脂肪环或芳香环构成的末端烯烃；所述的有机胺，可以是由脂肪链或脂肪环构成的有机胺。
3.如权利要求1所述的制备β-氨基醇的方法，其特征在于，以烯烃1为原料，首先加入二溴海因，然后再加入有机胺R2R3NH，得到相应的β-氨基醇2；
Figure FDA0002314126040000011
其中，R选自C1-C20烷基、取代基取代或未取代的C5-C20芳基，或上述R任选的可与烯基成取代基取代或未取代的环，所述取代基选自C1-C20烷基、卤素、硝基、羟基、C1-C20烷氧基、C1-C20烷氧基C1-C20烷基、羟基C1-C20烷基；
R2和R3各自独立地选自H、C1-C20烷基，或R2和R3可与N形成取代基取代或未取代的5-6元饱和杂环，所述取代基选自C1-C20烷基。
4.如权利要求3所述的制备β-氨基醇的方法，其特征在于，其中，R选自C1-C6烷基、取代基取代或未取代的苯基或萘基，或R与烯基形成取代基取代或未取代的四氢萘或茚，所述取代基选自C1-C6烷基、卤素、硝基；R2和R3各自独立地选自H、C1-C6烷基，或R2和R3可与N形成取代基取代或未取代的5-6元饱和杂环，所述取代基选自C1-C6烷基。
5.如权利要求3所述的制备β-氨基醇的方法，其特征在于，R2和R3各自独立地选自H、甲基、乙基、丙基、叔丁基，或R2R3NH为4-甲基哌啶或哌啶。
6.如权利要求1-5任一项所述的制备β-氨基醇的方法，其特征在于，所述反应溶剂体系为丙酮--水、乙腈--水、1,4-二氧六环--水、N,N-二甲基甲酰胺--水中的一种或它们的混合物。
7.如权利要求1-5任一项所述的制备β-氨基醇的方法，其特征在于，所述反应溶剂体系有机溶剂--水的体积比为1:1～20:1。
8.如权利要求1-5任一项所述的制备β-氨基醇的方法，其特征在于，末端烯烃与二溴海因的摩尔比为1:0.1～1:1。
9.如权利要求1-5任一项所述的制备β-氨基醇的方法，其特征在于，其中有机胺与末端烯烃的摩尔比为1:1～10:1。
10.如权利要求1-5任一项所述的制备β-氨基醇的方法，其特征在于，反应时间为0.5～48小时。
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