JPH0569818B2 - - Google Patents
Info
- Publication number
- JPH0569818B2 JPH0569818B2 JP62153038A JP15303887A JPH0569818B2 JP H0569818 B2 JPH0569818 B2 JP H0569818B2 JP 62153038 A JP62153038 A JP 62153038A JP 15303887 A JP15303887 A JP 15303887A JP H0569818 B2 JPH0569818 B2 JP H0569818B2
- Authority
- JP
- Japan
- Prior art keywords
- hydroxybutyronitrile
- chloro
- epichlorohydrin
- reaction
- chem
- 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 - Lifetime
Links
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- LHBPNZDUNCZWFL-UHFFFAOYSA-N 4-chloro-3-hydroxybutanenitrile Chemical compound ClCC(O)CC#N LHBPNZDUNCZWFL-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- -1 alkali metal cyanide Chemical class 0.000 claims description 4
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical group [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 229960001518 levocarnitine Drugs 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- LHBPNZDUNCZWFL-SCSAIBSYSA-N (3r)-4-chloro-3-hydroxybutanenitrile Chemical compound ClC[C@H](O)CC#N LHBPNZDUNCZWFL-SCSAIBSYSA-N 0.000 description 3
- BYJAJQGCMSBKPB-UHFFFAOYSA-N 3-hydroxybutanenitrile Chemical compound CC(O)CC#N BYJAJQGCMSBKPB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- BRLQWZUYTZBJKN-VKHMYHEASA-N (-)-Epichlorohydrin Chemical compound ClC[C@H]1CO1 BRLQWZUYTZBJKN-VKHMYHEASA-N 0.000 description 2
- YQGDEPYYFWUPGO-GSVOUGTGSA-N (3r)-4-amino-3-hydroxybutanoic acid Chemical compound NC[C@H](O)CC(O)=O YQGDEPYYFWUPGO-GSVOUGTGSA-N 0.000 description 2
- NHSSTOSZJANVEV-UHFFFAOYSA-N 2-hydroxybutanenitrile Chemical compound CCC(O)C#N NHSSTOSZJANVEV-UHFFFAOYSA-N 0.000 description 2
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 2
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229960004203 carnitine Drugs 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- YQGDEPYYFWUPGO-UHFFFAOYSA-N gamma-amino-beta-hydroxybutyric acid Chemical compound [NH3+]CC(O)CC([O-])=O YQGDEPYYFWUPGO-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BAPRUDZDYCKSOQ-RITPCOANSA-N (2s,4r)-1-acetyl-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound CC(=O)N1C[C@H](O)C[C@H]1C(O)=O BAPRUDZDYCKSOQ-RITPCOANSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 125000001549 ceramide group Chemical group 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- FJMMZJZTJGGXHX-UHFFFAOYSA-N potassium sodium dicyanide Chemical compound [K+].[C-]#N.[Na+].[C-]#N FJMMZJZTJGGXHX-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は医薬品である(R)−カルニチン及び(R)−
４−アミノ−３−ヒドロキシ酪酸を合成するため
の中間体として有用な(R)−４−クロル−３−ヒド
ロキシブチロニトリルの製法に関する。[Detailed Description of the Invention] (Industrial Application Field) The present invention is a pharmaceutical product (R)-carnitine and (R)-
The present invention relates to a method for producing (R)-4-chloro-3-hydroxybutyronitrile, which is useful as an intermediate for synthesizing 4-amino-3-hydroxybutyric acid.
（従来の技術とその問題点）
(R)−４−アミノ−３−ヒドロキシ酪酸は、その
薬効として脳代謝改善作用、脳血流量増加作用、
血圧降下作用、鎮静作用等がある。現在ラセミ体
で使用されているが、生物活性を示すのは(R)体で
あり、したがつて(R)体のみを高純度で得ることが
重要である。また(R)−カルニチンはビタミンBT
と称せられ、その優れた生物活性により、栄養
剤、医薬品として注目されている。(Prior art and its problems) (R)-4-Amino-3-hydroxybutyric acid has medicinal effects such as improving cerebral metabolism, increasing cerebral blood flow,
It has antihypertensive and sedative effects. Although the racemic form is currently used, it is the (R) form that exhibits biological activity, so it is important to obtain only the (R) form in high purity. Also, (R)-carnitine is a vitamin B T
Due to its excellent biological activity, it is attracting attention as a nutritional supplement and medicine.
(R)−カルニチンを得るために(R)−４−クロル−
３−ヒドロキシブチロニトリルを経由する方法と
してｄ−マンニトールを出発原料とする方法があ
る（特開昭57−16532号）。この方法によると出発
原料から目的中間体である(R)−４−クロル−３−
ヒドロキシブチロニトリルまで７段階を要し、総
収率が低く工業的生産には適さない。 To obtain (R)-carnitine, (R)-4-chlor-
As a method via 3-hydroxybutyronitrile, there is a method using d-mannitol as a starting material (Japanese Patent Application Laid-Open No. 16532/1983). According to this method, the desired intermediate (R)-4-chloro-3-
It takes seven steps to reach hydroxybutyronitrile, and the total yield is low, making it unsuitable for industrial production.
また、エピクロルヒドリンにシアン化ナトリウ
ムカリウムの水溶液と酢酸水溶液を同時添加して
中性条件下で反応させて４−クロル−３−ヒドロ
キシニトリルを得る方法があるが、収率が65.5％
と低収率である（J.Chem.Soc、3123頁（1950））。 Another method is to simultaneously add a sodium potassium cyanide aqueous solution and an acetic acid aqueous solution to epichlorohydrin and react under neutral conditions to obtain 4-chloro-3-hydroxynitrile, but the yield is 65.5%.
and low yield (J.Chem.Soc, p. 3123 (1950)).
他に(R)−カルニチン及び(R)−４−アミノ−３−
ヒドロキシ酪酸の製法として現在までに報告され
ているのは次のごとくである。 Also (R)-carnitine and (R)-4-amino-3-
The methods for producing hydroxybutyric acid that have been reported to date are as follows.
(i) Ｌ−アスコルビン酸を出発原料とする方法
（J.Am.Chem.Soc、第102巻、6304頁（1980））。(i) A method using L-ascorbic acid as a starting material (J.Am.Chem.Soc, Vol. 102, p. 6304 (1980)).
(ii) Ｌ−アラビノースを出発原料とする方法
（Acta.Chem.Scand.B、第37巻、344頁
（1983））。(ii) A method using L-arabinose as a starting material (Acta.Chem.Scand.B, Vol. 37, p. 344 (1983)).
(iii) シヤープレス酸化により不斉合成する方法
（J.Org.Chem.、第49巻、3707頁（1984））。(iii) A method of asymmetric synthesis by shear press oxidation (J.Org.Chem., Vol. 49, p. 3707 (1984)).
(iv) 酵素及び微生物を利用する方法（Tetrahed
−ron Lett、第25巻、5235頁（1984）、
Tetrahedron Lett、第26巻、101頁（1985）、
J.Bull.Soc.Chem：Fr、103頁（1980）、J.Am.
Chem.Soc、第105巻、5925頁（1983）、
Angew.Chem.Int.Ed.Engl、第23巻、151頁
（1984）、J.Am.Chem.Soc、第107巻、4028頁
（1985））。(iv) Methods using enzymes and microorganisms (Tetrahed
-ron Lett, Volume 25, Page 5235 (1984),
Tetrahedron Lett, Volume 26, Page 101 (1985),
J.Bull.Soc.Chem: Fr, 103 pages (1980), J.Am.
Chem.Soc, vol. 105, p. 5925 (1983),
Angew.Chem.Int.Ed.Engl, vol. 23, p. 151 (1984), J.Am.Chem.Soc, vol. 107, p. 4028 (1985)).
(v) （2S，4R）−Ｎ−アセチル−４−ヒドロキシ
プロリンを出発原料とする方法（Synthesis424
頁（1986））。(v) A method using (2S,4R)-N-acetyl-4-hydroxyproline as a starting material (Synthesis424
(1986)).
(vi) カルニチン及び４−アミノ−３−ヒドロキシ
酪酸誘導体の分割による方法（特公昭40−
3891、特公昭43−8248、特公昭43−26849、特
公昭43−26850、特公昭47−6609、特開昭51−
100026、特開昭52−133920、特開昭52−
133933、特開昭55−13299、特開昭59−
199666）。(vi) Method by resolution of carnitine and 4-amino-3-hydroxybutyric acid derivatives (Special Publication 1973-
3891, Special Publication No. 43-8248, Special Publication No. 43-26849, Special Publication No. 43-26850, Special Publication No. 47-6609, No. 51- Publication of Special Publication
100026, JP-A-52-133920, JP-A-52-
133933, JP-A-55-13299, JP-A-59-
199666).
以上の方法のうち(i)、(ii)は工程数の多いこと、
(iii)は生成物の光学純度の低いこと、(iv)は反応濃度
の低い、あるいは生成物の光学純度の低いこと、
(v)は出発原料が高価であること、(vi)は最高収率が
50％であつて得られた物質の50％は失われること
等の点でそれぞれ問題が残る。 Among the above methods, (i) and (ii) have a large number of steps;
(iii) is low optical purity of the product; (iv) is low reaction concentration or low optical purity of the product;
(v) is that the starting materials are expensive; (vi) is that the highest yield is
However, problems remain in that 50% of the obtained substance is lost.
（問題点を解決するための手段）
本発明者は上記の問題点を解決するために種々
検討を行つた結果、本発明を完成した。(Means for Solving the Problems) The present inventor has completed the present invention as a result of various studies to solve the above problems.
すなわち本発明はエピクロルヒドリンをPH8.0
〜10.0の弱塩基性条件下で青酸アルカリ金属塩と
反応させることを特徴とする４−クロル−３−ヒ
ドロキシブチロニトリルの製法である。 That is, the present invention uses epichlorohydrin at pH 8.0.
This is a method for producing 4-chloro-3-hydroxybutyronitrile, which is characterized by reacting it with an alkali metal cyanide salt under weak basic conditions of ~10.0%.
本発明方法によつて得られる(R)−４−クロル−
３−ヒドロキシブチロニトリルはトリメチルアミ
ンと反応させた後、酸化水分解により高純度の(R)
−カルニチンに変換することができ、またアンモ
ニアと反応させた後、酸加水分解により高純度の
(R)−４−アミノ−３−ヒドロキシ酪酸に変換でき
る点で有用な中間体である。 (R)-4-chloro- obtained by the method of the present invention
3-Hydroxybutyronitrile is reacted with trimethylamine and then converted to highly pure (R) by oxidative water decomposition.
- Can be converted to carnitine, and can also be purified with high purity by acid hydrolysis after reacting with ammonia.
It is a useful intermediate because it can be converted to (R)-4-amino-3-hydroxybutyric acid.
本発明方法はセラミ体のエピクロルヒドリンを
用いてセラミ体の４−クロル−３−ヒドロキシブ
チロニトリルを得ることもできるが、光学活性体
の原料を用いて光学活性体の製品を得ることが上
記の理由により特に有用である。 In the method of the present invention, it is also possible to obtain 4-chloro-3-hydroxybutyronitrile in a ceramide form using epichlorohydrin in a ceramic form, but it is possible to obtain an optically active product using a raw material for an optically active substance as described above. It is particularly useful for a number of reasons.
(R)−エピクロルヒドリンより(R)−４−クロル−
３−ヒドロキシブチロニトリルを合成する反応は
青酸の付加反応である。その反応条件としてPHの
調整が目的生成物の収率に大きく関係し、弱塩基
性下で反応を行う必要があり、最適のPHは8.0〜
10.0である。溶媒は水とアルコール類の混合溶媒
が好ましい。青酸アルカリ金属塩としてシアン化
カリウム、シアン化ナトリウムが好ましく、PH調
整用の酸としては酢酸が好ましい。反応温度は20
〜25℃が最適であり、1.5〜４時間で反応は終了
する。反応後溶液をエーテル抽出し、このエーテ
ル層を洗浄し乾燥後、溶媒を留去して得られた残
渣を減圧蒸溜して無色油状の(R)−４−クロル−３
−ヒドロキシブチロニトリルが得られる。 (R)-4-chloro- from (R)-epichlorohydrin
The reaction for synthesizing 3-hydroxybutyronitrile is an addition reaction of hydrocyanic acid. As for the reaction conditions, the adjustment of pH has a great influence on the yield of the target product, and the reaction must be carried out under weak basicity, and the optimal pH is 8.0 ~
It is 10.0. The solvent is preferably a mixed solvent of water and alcohol. Potassium cyanide and sodium cyanide are preferred as the alkali metal cyanide salt, and acetic acid is preferred as the acid for pH adjustment. The reaction temperature is 20
~25°C is optimal, and the reaction is complete in 1.5 to 4 hours. After the reaction, the solution was extracted with ether, the ether layer was washed and dried, the solvent was distilled off, and the resulting residue was distilled under reduced pressure to obtain (R)-4-chloro-3 as a colorless oil.
-Hydroxybutyronitrile is obtained.
実施例
この実施例において使用される光学活性なエピ
クロルヒドリンは本出願人の出願に係る特開昭61
−132196号、特公平１−55879号公報に記載の方
法により得られたものである。Example The optically active epichlorohydrin used in this Example is
-132196 and Japanese Patent Publication No. 1-55879.
(R)−エピクロルヒドリン（9.25ｇ100ｍmol）
をエタノール（21ml）に溶かし、室温で撹拌しな
がら、シアン化カリウム水溶液（9.90ｇ、150ｍ
mol、H2O35ml）と2.5N酢酸水溶液とを15分間同
時に滴下し、その際液性をPH8.0〜10.0、温度24
℃以下に保つた。さらに２時間撹拌を続けた。反
応後液をエーテルで抽出し、このエーテル層を飽
和食塩水により洗浄し、さらに硫酸マグネシウム
により乾燥後、溶媒を減圧下留去した。得られた
残渣を減圧蒸溜し（139〜141℃／13mmHg）、無色
油状の(R)−４−クロル−３−ヒドロキシブチロニ
トリル9.37ｇを得た（収率78.4％）。 (R)-Epichlorohydrin (9.25g100mmol)
was dissolved in ethanol (21 ml), and while stirring at room temperature, potassium cyanide aqueous solution (9.90 g, 150 ml) was added.
mol, H 2 O (35 ml) and a 2.5 N acetic acid aqueous solution were simultaneously added dropwise for 15 minutes, at a pH of 8.0 to 10.0 and a temperature of 24
It was kept below ℃. Stirring was continued for an additional 2 hours. The reaction solution was extracted with ether, and the ether layer was washed with saturated brine, dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was distilled under reduced pressure (139-141° C./13 mmHg) to obtain 9.37 g of (R)-4-chloro-3-hydroxybutyronitrile as a colorless oil (yield 78.4%).
〔α〕D＋17.25°（Ｃ、1.02、MeOH）
Ｈ−NMR（CDCl3）δ
2.70（2H、ｄ、Ｊ＝6.OHz、−ＣH2 −CH）
3.20〜3.45（1H、br、exchangeable with D20、
−ＯＨ）
3.62（2H、ｄ、Ｊ＝5.4Hz、−ＣH2 −Cl
3.95〜4.30（1H、ｍ、−ＣＨ（OH）−）
IRνmax（cm-1）：3432（OH）、2260（CN）
（発明の効果）
本発明によつて得られた(R)−４−クロル−３−
ヒドロキシブチロニトリルは、前記のごとく高純
度の(R)−カルニチンあるいは(R)−４−アミノ−３
−ヒドロキシ酪酸に変換できる。中性条件下で同
様の反応を、行う従来方法に比較し、本発明方法
によれば高純度の(R)−４−クロル−３−ヒドロキ
シブチロニトリルを75〜80％の収率で得られるの
で、10％以上の収率の向上が可能である。[α] D +17.25° (C, 1.02, MeOH) H-NMR (CDCl 3 ) δ 2.70 (2H, d, J = 6.OHz, -CH 2 -CH) 3.20-3.45 (1H, br, exchangeable with D20 ,
-OH ) 3.62 (2H, d, J=5.4Hz, -CH2 - Cl 3.95~4.30 (1H, m, -CH (OH)-) IRνmax (cm -1 ): 3432 (OH), 2260 (CN) (Effect of the invention) (R)-4-chloro-3- obtained by the present invention
Hydroxybutyronitrile is highly purified (R)-carnitine or (R)-4-amino-3 as mentioned above.
- Can be converted to hydroxybutyric acid. Compared to the conventional method in which a similar reaction is carried out under neutral conditions, the method of the present invention yields highly purified (R)-4-chloro-3-hydroxybutyronitrile with a yield of 75 to 80%. Therefore, it is possible to improve the yield by more than 10%.
Claims (1)
性条件下で青酸アルカリ金属塩と反応させること
を特徴とする４−クロル−３−ヒドロキシブチロ
ニトリルの製法。 ２ エピクロルヒドリン及び４−クロル−３−ヒ
ドロキシブチロニトリルが光学活性体である特許
請求の範囲第１項記載の製法。 ３ 青酸アルカリ金属塩がシアン化カリウム又は
シアン化ナトリウムである特許請求の範囲第１項
もしくは第２項記載の製法。[Scope of Claims] 1. A method for producing 4-chloro-3-hydroxybutyronitrile, which comprises reacting epichlorohydrin with an alkali metal cyanide under weakly basic conditions of pH 8.0 to 10.0. 2. The manufacturing method according to claim 1, wherein epichlorohydrin and 4-chloro-3-hydroxybutyronitrile are optically active substances. 3. The production method according to claim 1 or 2, wherein the alkali metal cyanide salt is potassium cyanide or sodium cyanide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15303887A JPS63316758A (en) | 1987-06-18 | 1987-06-18 | Production of 4-chloro-3-hydroxybutyronitrile |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15303887A JPS63316758A (en) | 1987-06-18 | 1987-06-18 | Production of 4-chloro-3-hydroxybutyronitrile |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63316758A JPS63316758A (en) | 1988-12-26 |
| JPH0569818B2 true JPH0569818B2 (en) | 1993-10-01 |
Family
ID=15553617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15303887A Granted JPS63316758A (en) | 1987-06-18 | 1987-06-18 | Production of 4-chloro-3-hydroxybutyronitrile |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63316758A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009122997A1 (en) | 2008-04-02 | 2009-10-08 | 株式会社カネカ | Method of producing (s)-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5210031A (en) * | 1989-07-20 | 1993-05-11 | Nitto Chemical Industry Co., Ltd. | Process for the production of R(-)-4-halo-3-hydroxybutyronitrile |
| JPH04124157A (en) * | 1990-09-12 | 1992-04-24 | Daiso Co Ltd | Production of optically active 4-chloro-3-hydroxybutanoic acid and its ester |
| JP2734876B2 (en) * | 1992-05-14 | 1998-04-02 | ダイソー株式会社 | Method for producing optically active 4-chloro-3-hydroxybutyronitrile |
| JPH11193285A (en) * | 1997-12-26 | 1999-07-21 | Dai Ichi Seiyaku Co Ltd | Production of bicyclic heterocyclic thiol compound |
| KR100491809B1 (en) * | 2002-11-27 | 2005-05-27 | 주식회사 알에스텍 | Production of 3-Substituted-3'-hydroxypropionitrile |
| KR20040090062A (en) * | 2003-04-16 | 2004-10-22 | 주식회사 엘지생명과학 | Process for preparing 4-chloro-3-hydroxybutanoic acid ester |
| JP4550107B2 (en) * | 2004-03-13 | 2010-09-22 | アールエステック コーポレイション | Method for producing 3-substituted-3'-hydroxypropionitrile |
| JP2008067626A (en) * | 2006-09-13 | 2008-03-27 | Mitsubishi Rayon Co Ltd | Method for producing 4-halo-3-hydroxybutyramide |
| CN100408555C (en) * | 2006-09-15 | 2008-08-06 | 四川省天然气化工研究院 | Preparation method of 4-chlorine-3-hydroxybutyronitrile |
| JP2008148637A (en) * | 2006-12-19 | 2008-07-03 | Mitsubishi Rayon Co Ltd | Method for producing 4-halo-3-hydroxybutyramide |
-
1987
- 1987-06-18 JP JP15303887A patent/JPS63316758A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009122997A1 (en) | 2008-04-02 | 2009-10-08 | 株式会社カネカ | Method of producing (s)-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63316758A (en) | 1988-12-26 |
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