[go: up one dir, main page]

CN103613534B - 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

Info

Publication number
CN103613534B
CN103613534B CN201310622540.9A CN201310622540A CN103613534B CN 103613534 B CN103613534 B CN 103613534B CN 201310622540 A CN201310622540 A CN 201310622540A CN 103613534 B CN103613534 B CN 103613534B
Authority
CN
China
Prior art keywords
nicotinic acid
dihydroxyl
fluoro
reaction
synthetic method
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201310622540.9A
Other languages
English (en)
Other versions
CN103613534A (zh
Inventor
徐骏
张浩波
吴妤萱
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CHEMFUTURE PHARMATECH (JIANGSU) Ltd
Original Assignee
CHEMFUTURE PHARMATECH (JIANGSU) Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by CHEMFUTURE PHARMATECH (JIANGSU) Ltd filed Critical CHEMFUTURE PHARMATECH (JIANGSU) Ltd
Priority to CN201310622540.9A priority Critical patent/CN103613534B/zh
Publication of CN103613534A publication Critical patent/CN103613534A/zh
Application granted granted Critical
Publication of CN103613534B publication Critical patent/CN103613534B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • 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 (3)

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1：75。
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。
CN201310622540.9A 2013-11-30 2013-11-30 一种2,4-二羟基烟酸的合成方法 Expired - Fee Related CN103613534B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201310622540.9A CN103613534B (zh) 2013-11-30 2013-11-30 一种2,4-二羟基烟酸的合成方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201310622540.9A CN103613534B (zh) 2013-11-30 2013-11-30 一种2,4-二羟基烟酸的合成方法

Publications (2)

Publication Number Publication Date
CN103613534A CN103613534A (zh) 2014-03-05
CN103613534B true CN103613534B (zh) 2015-09-30

Family

ID=50164264

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310622540.9A Expired - Fee Related CN103613534B (zh) 2013-11-30 2013-11-30 一种2,4-二羟基烟酸的合成方法

Country Status (1)

Country Link
CN (1) CN103613534B (zh)

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

Patent 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
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

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
4-羟基-2-吡啶酮类化合物的合成研究进展;赵圣印等;《有机化学》;20120415;第32卷;第651-660页 *
SPF32629A and SPF32629B: Enantioselective synthesis, determination of absolute configuration, cytotoxicity and antibacterial evaluation;20110228;《European Journal of Medicinal Chemistry》;20110228;第46卷;第1807页6.2-6.3节、第1804页流程图1 *
Spontaneous polymerization of cyanoacetyl chloride, a simple synthesis, of the alkaloid ricinine;Schroeter, G.等;《Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen》;19321231;第65B卷;第432页第1段、流程图1 *

Also Published As

Publication number Publication date
CN103613534A (zh) 2014-03-05

Similar Documents

Publication Publication Date Title
MY170520A (en) Method of synthesizing thyroid hormone analogs and polymorphs thereof
CN105367526A (zh) 一种高纯度正丁基苯酞的制备方法
CN103641722A (zh) 一种邻硝基溴苄的生产方法
UA104684C2 (ru) Промежуточное соединение для получения агомелатина (варианты) и способ его получения (варианты)
CN103613534B (zh) 一种2,4-二羟基烟酸的合成方法
CN105198707B (zh) 4‑联苯甲醇的合成方法
CN103214446A (zh) 一种色满酮衍生物的不对称合成方法
CN103113227A (zh) 3-甲氧基丙烯酸甲酯的制备方法
CN106588698B (zh) 一种N-Boc联苯丙氨醛的制备方法
CN105646532B (zh) 一种2‑叔丁氧羰基‑10‑羰基‑8‑氧代‑2,11‑二氮杂螺[5.6]十二烷的合成方法
CN103613530B (zh) 一种芴甲氧羰基-3-哌啶醇的合成方法
CN103449992A (zh) 一种合成溴丁酮的方法
CN106905205B (zh) 一种一步构筑c-o和c-s键双官能化产物及其制备方法
CN105153210A (zh) 一种异丁基硼酸的制备方法
CN104059094B (zh) 9-硼杂双环[3.3.1]壬烷二聚体的合成方法
CN103724212B (zh) 一种手性（s）-苯乙胺盐酸盐氯化钴配合物晶体
JP6052949B2 (ja) フルオレンからの９−フルオレノンの製造方法
CN104447776A (zh) 一种新型杂环有机化合物及其制备方法
Xiong et al. An Improved Large-scale Preparation of Roche Lactone, an Intermediate for the Synthesis of (+)-Biotin
CN110407676B (zh) 一种二苯乙二酮类化合物的合成方法及应用
CN102286052B (zh) 一种孕烯酮醇化合物的合成方法
CN103804150A (zh) 一种3,4-二甲氧基苄基溴的制备方法
CN107445791A (zh) 一种番茄红素的制备方法
CN103772382A (zh) 一种6-溴-8-羟基-咪唑并（1,2a）吡啶盐酸盐及其合成方法
CN105001149A (zh) 一种琥珀酸多西拉敏中间体2-吡啶基苯基甲基甲醇的制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20150930

Termination date: 20171130