CN103613534A - 一种2,4-二羟基烟酸的合成方法 - Google Patents

一种2,4-二羟基烟酸的合成方法 Download PDF

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CN103613534A
CN103613534A CN201310622540.9A CN201310622540A CN103613534A CN 103613534 A CN103613534 A CN 103613534A CN 201310622540 A CN201310622540 A CN 201310622540A CN 103613534 A CN103613534 A CN 103613534A
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nicotinic acid
synthetic method
dihydroxyl
reaction
fluoro
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CN103613534B (zh
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徐骏
张浩波
吴妤萱
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CHEMFUTURE PHARMATECH (JIANGSU) Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation

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  • Pyridine Compounds (AREA)

Abstract

本发明公开了一种2,4-二羟基烟酸的合成方法，以2-氟-4-甲氧基烟酸和BBr3为反应原料，以乙腈为反应溶剂，在室温下反应2.5-3小时，水淬灭反应，生成2,4-二羟基烟酸，所述2-氟-4-甲氧基烟酸与BBr3的摩尔比为1：50-100。本发明提供的2,4-二羟基烟酸的合成方法，反应条件简单易操作，路线短，且反应过程易于控制，反应收率高，能够真正实现工业化大规模生产。

Description

一种2,4-二羟基烟酸的合成方法
技术领域
    本发明涉及一种2,4-二羟基烟酸的合成方法，属于有机合成领域。
背景技术
2，4-二羟基吡啶是合成多种化合物的重要中间体，2,4-二羟基烟酸是合成2,4-二羟基吡啶的重要原料。以往的化学合成方法往往收率较低，不适合工业化大规模生产。
发明内容
本发明要解决的技术问题是克服现有的缺陷，提供了一种合成效率高，可实现大规模工业化生产的2,4-二羟基烟酸的合成方法。
本发明的目的通过以下技术方案来具体实现：
一种2,4-二羟基烟酸的合成方法，以2-氟-4-甲氧基烟酸和BBr3为反应原料，以乙腈为反应溶剂，在室温下反应2.5-3小时，水淬灭反应，生成2,4-二羟基烟酸，所述2-氟-4-甲氧基烟酸与BBr3的摩尔比为1：50-100。
反应式如下：
。
具体操作为：将2-氟-4-甲氧基烟酸溶于乙腈，冰水浴降温至零度，缓慢滴入BBr3，室温搅拌3h，加入水淬灭反应，用乙酸乙酯萃取，减压蒸馏得到粗品，通过柱层析得到2,4-二羟基烟酸。
优选的，
所述2-氟-4-甲氧基烟酸：乙腈为1g:20mL；
所述2-氟-4-甲氧基烟酸与BBr3的摩尔比为1：75。 
本发明的有益效果：
    本发明提供的2,4-二羟基烟酸的合成方法，反应条件简单易操作，路线短，且反应过程易于控制，反应收率高，能够真正实现工业化大规模生产。
附图说明
附图用来提供对本发明的进一步理解，并且构成说明书的一部分，与本发明的实施例一起用于解释本发明，并不构成对本发明的限制。在附图中：
图1是本发明实施例1制备得到的2,4-二羟基烟酸的HNMR图谱。
具体实施方式
以下结合附图对本发明的优选实施例进行说明，应当理解，此处所描述的优选实施例仅用于说明和解释本发明，并不用于限定本发明。
实施例1：
2-氟-4-甲氧基烟酸（5g，0.029mol）溶于100ml乙腈，冰水浴降温至零度，缓慢滴入BBr3（21.85g，3mol）,室温搅拌3h，加入20ml水淬灭反应，用100ml乙酸乙酯萃取3次，减压蒸馏得到粗品，通过柱层析得到2,4-二羟基烟酸2.5g，收率55.2%。
产物HNMR图谱参见附图1：产物结构中含有五组氢原子，且其化学位移与产品结构吻合，化学位移在15.90ppm处的单峰为3位-COOH的H峰，13.26ppm和12.77处的单峰分别为2位和4位的OH的H峰，7.82ppm处的单峰为5位CH的H峰，6.35ppm处的单峰为6位CH的H峰。
实施例2：
2-氟-4-甲氧基烟酸（5g，0.029mol）溶于100ml乙腈，冰水浴降温至零度，缓慢滴入BBr3（15.30g，2.1mol）,室温搅拌3h，加入15ml水淬灭反应，用100ml乙酸乙酯萃取3次，减压蒸馏得到粗品，通过柱层析得到2,4-二羟基烟酸3.4g，收率75.6%。
实施例3：
2-氟-4-甲氧基烟酸（5g，0.029mol）溶于100ml乙腈，冰水浴降温至零度，缓慢滴入BBr3（10.93g，1.5mol）,室温搅拌3h，加入10ml水淬灭反应，用100ml乙酸乙酯萃取3次，减压蒸馏得到粗品，通过柱层析得到2,4-二羟基烟酸2.9g，收率65.5%。
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。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 (4)

1.一种2,4-二羟基烟酸的合成方法，其特征在于：以2-氟-4-甲氧基烟酸和BBr3为反应原料，以乙腈为反应溶剂，在室温下反应2.5-3小时，水淬灭反应，生成2,4-二羟基烟酸，所述2-氟-4-甲氧基烟酸与BBr3的摩尔比为1：50-100。
2.根据权利要求1所述的2,4-二羟基烟酸的合成方法，其特征在于：具体操作为：将2-氟-4-甲氧基烟酸溶于乙腈，冰水浴降温至零度，缓慢滴入BBr3，室温搅拌3h，加入水淬灭反应，用乙酸乙酯萃取，减压蒸馏得到粗品，通过柱层析得到2,4-二羟基烟酸。
3.根据权利要求1所述的2,4-二羟基烟酸的合成方法，其特征在于：所述2-氟-4-甲氧基烟酸：乙腈为1g:20mL。
4.根据权利要求1-3任一项所述的2,4-二羟基烟酸的合成方法，其特征在于：所述2-氟-4-甲氧基烟酸与BBr3的摩尔比为1：75。
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002030407A1 (en) * 2000-10-13 2002-04-18 Astrazeneca Ab ESTROGEN RECEPTOR-β LIGANDS
WO2012116254A2 (en) * 2011-02-25 2012-08-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chrysophaentin analogs that inhibit ftsz protein
CN102993088A (zh) * 2012-12-31 2013-03-27 东华大学 一种4-羟基-2-吡啶酮的制备方法
CN103360308A (zh) * 2012-03-28 2013-10-23 孙伟新 1,4-二羟基-6-甲基-2-吡啶酮类化合物及其制备方法和用途

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* Cited by examiner, † Cited by third party
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WO2002030407A1 (en) * 2000-10-13 2002-04-18 Astrazeneca Ab ESTROGEN RECEPTOR-β LIGANDS
WO2012116254A2 (en) * 2011-02-25 2012-08-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chrysophaentin analogs that inhibit ftsz protein
CN103360308A (zh) * 2012-03-28 2013-10-23 孙伟新 1,4-二羟基-6-甲基-2-吡啶酮类化合物及其制备方法和用途
CN102993088A (zh) * 2012-12-31 2013-03-27 东华大学 一种4-羟基-2-吡啶酮的制备方法

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SCHROETER, G.等: "Spontaneous polymerization of cyanoacetyl chloride, a simple synthesis, of the alkaloid ricinine", 《BERICHTE DER DEUTSCHEN CHEMISCHEN GESELLSCHAFT [ABTEILUNG] B: ABHANDLUNGEN》, vol. 65, 31 December 1932 (1932-12-31) *
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