JPS60178845A - Production of 3-nitratopropanol - Google Patents
Production of 3-nitratopropanolInfo
- Publication number
- JPS60178845A JPS60178845A JP59033247A JP3324784A JPS60178845A JP S60178845 A JPS60178845 A JP S60178845A JP 59033247 A JP59033247 A JP 59033247A JP 3324784 A JP3324784 A JP 3324784A JP S60178845 A JPS60178845 A JP S60178845A
- Authority
- JP
- Japan
- Prior art keywords
- reducing agent
- borohydride
- lower alkyl
- aluminum hydride
- ether
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 15
- 239000002253 acid Substances 0.000 claims abstract description 12
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract description 7
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000012442 inert solvent Substances 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 6
- 150000002148 esters Chemical class 0.000 abstract description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 abstract description 4
- 239000001110 calcium chloride Substances 0.000 abstract description 2
- 229910001628 calcium chloride Inorganic materials 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 abstract 2
- 229910052782 aluminium Inorganic materials 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 abstract 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 abstract 2
- WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 abstract 1
- 241000045500 Diseae Species 0.000 abstract 1
- WOWBFOBYOAGEEA-UHFFFAOYSA-N diafenthiuron Chemical compound CC(C)C1=C(NC(=S)NC(C)(C)C)C(C(C)C)=CC(OC=2C=CC=CC=2)=C1 WOWBFOBYOAGEEA-UHFFFAOYSA-N 0.000 abstract 1
- 235000019260 propionic acid Nutrition 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- RVGLEPQPVDUSOJ-UHFFFAOYSA-N 2-Methyl-3-hydroxypropanoate Chemical compound COC(=O)CCO RVGLEPQPVDUSOJ-UHFFFAOYSA-N 0.000 description 2
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- -1 3-hydroxypropyl tetraphosphate ethyl ester Chemical compound 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- BNOODXBBXFZASF-UHFFFAOYSA-N [Na].[S] Chemical compound [Na].[S] BNOODXBBXFZASF-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001622 calcium bromide Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Inorganic materials [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】 関する。[Detailed description of the invention] related.
循環器疾患治療剤として有用な、２，６−ジメチル−４
−（３−ニトロフェニル） １，４−ジヒド四ビリジン
ー３，５ージカルボン酸２−（２−ニトラトプロビル）
エステル−５−（３−ニトラトプロビル）エステル［特
開昭５８−１８５５６２号公報記載］の合成原料の一つ
である１セト酢酸３−ニトラトブＵビルエステルは３−
ニドラドプロパノールから導くことができる。2,6-dimethyl-4 useful as a therapeutic agent for cardiovascular diseases
-(3-nitrophenyl) 1,4-dihydrotetrapyridine-3,5-dicarboxylic acid 2-(2-nitratoprovir)
1-cetoacetic acid 3-nitratoprobyl ester, which is one of the raw materials for the synthesis of ester-5-(3-nitratoprobyl) ester [described in JP-A-58-185562], is 3-nitratoprobyl ester.
It can be derived from nidradopropanol.
３−ニドラドプロパノールは、３−ハロゲノプロパノー
ルに硝酸銀を作用することによって得ろことができるが
、この方法は原料として高価な銀塩を用いるためコスト
が高くなり、実用上好ましくない。3-nidoradopropanol can be obtained by reacting 3-halogenopropanol with silver nitrate, but this method uses expensive silver salt as a raw material, resulting in high costs and is not preferred in practice.
本発明者らは、従来法の欠点を解消すべく鋭意研究の結
果、３−ニドラドプロピオン酸低級アルキルエステルを
安価な還元剤を用いて還元することにより低コストで３
−ニドラドプロパノールを得る乙とに成功し、本発明を
完成した。As a result of intensive research in order to eliminate the drawbacks of conventional methods, the present inventors have succeeded in reducing 3-nidoradopropionic acid lower alkyl ester using an inexpensive reducing agent.
- We succeeded in obtaining nidradopropanol and completed the present invention.
本発明の方法は、不活性溶媒中、３−ニドラドプロピオ
ン酸低級アルキルエステルを水素化ホウ素系または水素
化アルミニウム系還元剤を用いて還元する３−ニドラド
プロパノールの製造法である。The method of the present invention is a method for producing 3-nidoradopropanol, in which lower alkyl 3-nidoradopropionic acid ester is reduced using a borohydride-based or aluminum hydride-based reducing agent in an inert solvent.
ここにおいて、３−ニドラドプロピオン酸低級アルキル
エステルの低級アルキルは炭素数１〜３個の低級アルキ
ルを意味する。Here, the lower alkyl of the 3-nidradopropionic acid lower alkyl ester means a lower alkyl having 1 to 3 carbon atoms.
水素化ホウ素系還元剤とは、ＮａＢＨ４゜Ｃａ （、Ｂ
Ｈａ） ２． ＮａＢ１（Ａ−ＬｉＣｊ。The borohydride reducing agent is NaBH4゜Ca (, B
Ha) 2. NaB1(A-LiCj.
ＮａＢＨ４−ＬｉＢｒ、ＮａＢＨｄ−ＣａＣｌ２゜Ｎａ
ＢＨ４−ＭｇＣｌ２．ＮａＢＨｊ−ＺｎＣｌ２゜ＮａＢ
ＨＪ−ＴｉＣｊ１４．ＮａＢＨ４−ＣａＢｒ２゜ＮａＢ
Ｈ４−ＭｇＢｒ２． ＮａＢＨ［０ＣＨ（ＣＨ３）２］
３などをいい、水素化アルミニウム還元剤とはＡＪＨ［
ＣＨ２ＣＨ（ＣＨ３１２］２゜ＮａＡｌＨ４（ＯＣＨ２
ＣＨ２０ＣＨ３）２などをいう。NaBH4-LiBr, NaBHd-CaCl2゜Na
BH4-MgCl2. NaBHj-ZnCl2゜NaB
HJ-TiCj14. NaBH4-CaBr2゜NaB
H4-MgBr2. NaBH[0CH(CH3)2]
3, etc., and aluminum hydride reducing agent is AJH [
CH2CH(CH312)2゜NaAlH4(OCH2
CH20CH3)2 etc.
不活性溶媒とは、本反応に関与しない溶媒であればよい
が、水素化ホウ素系還元剤を使用する場合は水またはメ
タノール、エタノール、イソプロパツールなどのアルコ
ール類、ジメトキシエタン。The inert solvent may be any solvent that does not participate in this reaction, but when using a borohydride reducing agent, it may be water, alcohols such as methanol, ethanol, isopropanol, or dimethoxyethane.
ジオキサン、ジグライム、テトラヒドロフランなどのエ
ーテル類などの使用が好ましく、水素化アルミニウム系
還元剤を使用する場合はエーテル。Ethers such as dioxane, diglyme, and tetrahydrofuran are preferably used, and ether is used when an aluminum hydride reducing agent is used.
テトラヒドロフラン、ベンゼン、トルエンなどの使用が
好ましい。Preference is given to using tetrahydrofuran, benzene, toluene and the like.
還元反応は、水素化ホウ素系還元剤を使用する場合は２
０〜１２０℃で行い、水素化アルミニウム系還元剤を使
用する場合は一５０〜３０℃で行う。The reduction reaction is 2 when using a borohydride reducing agent.
It is carried out at 0 to 120°C, and when an aluminum hydride reducing agent is used, it is carried out at -50 to 30°C.
本発明の方法において最も好適な還元剤はＮａＢＨ４−
ＣＪＩＣＪ２であり、最も望ましい３−ニドラドプロピ
オン酸低級アルキルエステル；よ３−ニドラドプロピオ
ン酸メチルエステルである。The most preferred reducing agent in the method of the present invention is NaBH4-
CJICJ2 is the most preferred 3-nidoradopropionic acid lower alkyl ester; 3-nidoradopropionic acid methyl ester.
この場合は、反応時間が短かく、高純度の目的物を高収
率で得ることができる。In this case, the reaction time is short and the target product of high purity can be obtained in high yield.
以上の如く、本発明の方法は硝酸銀のような高価な原料
を使用する必要がなく、安価な原料を使用して本発明の
目的物を高収率且つ低コストで得ることを可能にする。As described above, the method of the present invention does not require the use of expensive raw materials such as silver nitrate, and makes it possible to obtain the object of the present invention in high yield and at low cost using inexpensive raw materials.
以下、参考例と実施例を挙げて本発明を具体的に説明す
る。Hereinafter, the present invention will be specifically explained with reference to reference examples and examples.
参考例１
（１１メタノール１．５ｊｌ、水１３４１の混液に塩酸
ガス４５４ｇを吹き込み、これに室温でエチレンシアノ
ヒドリン４４２ｇを加え、４０℃で２時間、更に室温で
４０時間攪拌したのち、重ソウ５００６を加えて中和し
、減圧ろ過した。Reference Example 1 (454 g of hydrochloric acid gas was blown into a mixture of 1.5 jl of 11 methanol and 1341 g of water, and 442 g of ethylene cyanohydrin was added thereto at room temperature. After stirring at 40°C for 2 hours and further at room temperature for 40 hours, heavy sodium sulfur 5006 was added. The mixture was added to neutralize and filtered under reduced pressure.
不溶物をア七トンで洗い、その洗液をろ液と合わせ、溶
媒を留去後、蒸留し、３−ヒドロキシプロピオン酸メチ
ルエステル５４４ ｇ （収率８４．０％）を得た。The insoluble matter was washed with amethane, the washing liquid was combined with the filtrate, the solvent was distilled off, and the mixture was distilled to obtain 544 g (yield: 84.0%) of methyl 3-hydroxypropionate.
ｂ、ｐ、７１〜７５℃／ １７ ＋ｍｍＨｇ（２１６＆
！！酸２９７ｇに発煙硝酸（ｄ ｔ、５２）２９７ｇを
−５〜−１０℃に冷却下４０分間で滴下し、更に同温度
を保ちつつ、３−ヒドロキシプロピオン酸メチルエステ
ル２４６ｇを３０分間で滴下した。０℃で２時間攪拌後
２ 、５ ｋｇの氷にあけ、エーテル１１を加えて抽出
しｔこ。水槽を更にエーテル０．５ｊｌで抽出し、エー
テル層を合わせ、水、飽和型ソウ水、飽和食塩水の順で
洗浄し、無水硫酸ナトリウムで乾燥し、溶媒を留去後蒸
留し３−ニドラドプロピオンメチルエステル３２０ｇ（
収率９０８％）を得た。b, p, 71-75℃/17 +mmHg (216&
! ! To 297 g of acid, 297 g of fuming nitric acid (dt, 52) was added dropwise over 40 minutes while cooling to -5 to -10°C, and further, while maintaining the same temperature, 246 g of methyl 3-hydroxypropionate was added dropwise over 30 minutes. After stirring at 0°C for 2 hours, the mixture was poured into 2.5 kg of ice, and extracted with ether 11. The aquarium was further extracted with 0.5 liters of ether, the ether layers were combined, washed successively with water, saturated sodium chloride water, and saturated brine, dried over anhydrous sodium sulfate, and after distilling off the solvent, 3-nidorado Propion methyl ester 320g (
A yield of 908%) was obtained.
ｂ、９．５９ 〜６２ ℃／ ０．５−一〇ｇ参考物２
濃硫酸３７８ｇに発煙硝酸（ｄ １．５２）３７８ｇを
−５〜−１０℃に冷却下滴下し、更に同温度を保ちつつ
、エチレンシアノヒドリン２１３ｇを２０分間で滴下し
た。−１０〜０℃で１時間攪拌後、３ｋｇの氷にあけ、
エーテル１．５ｊｌで抽出した。エーテル層を水、飽和
型ソウ水、飽和食塩水で順次洗浄し、無水硫酸ナトリウ
ムで乾燥後ろ過した。このろ液にメタノール７０ｇを加
え、−１０℃に冷却下、乾燥塩酸ガスを飽和するまで吹
き込み、更に一１０〜θ℃で１３時間攪拌した。析出し
た結晶をろ取し、エーテル１１で洗浄後結晶をエーテル
１１に加え、水冷下これに１．６Ｎ塩酸５００ｓ＋１を
加えて２時間攪拌した。b, 9.59 to 62 °C / 0.5 to 10 g Reference material 2 378 g of fuming nitric acid (d 1.52) was added dropwise to 378 g of concentrated sulfuric acid while cooling to -5 to -10 °C, and the temperature was further maintained. At the same time, 213 g of ethylene cyanohydrin was added dropwise over 20 minutes. After stirring at -10 to 0℃ for 1 hour, pour into 3 kg of ice.
Extracted with 1.5jl of ether. The ether layer was washed successively with water, saturated sodium chloride water, and saturated brine, dried over anhydrous sodium sulfate, and filtered. 70 g of methanol was added to this filtrate, and while cooling to -10°C, dry hydrochloric acid gas was blown into the mixture until it was saturated, and the mixture was further stirred at -10°C to θ°C for 13 hours. The precipitated crystals were collected by filtration, washed with ether 11, added to ether 11, and 500 s+1 of 1.6N hydrochloric acid was added thereto under water cooling, followed by stirring for 2 hours.
このエーテル溶液を飽和型ソウ水、飽和食塩水で順次洗
浄し、無水硫酸ナトリウムで乾燥し、溶媒を留去後蒸留
し、３−ニドラドプロピオン酸メチル３０３ｇ （収率
６７．８％）を得た。This ether solution was washed successively with saturated sodium chloride water and saturated brine, dried over anhydrous sodium sulfate, and distilled after distilling off the solvent to obtain 303 g of methyl 3-nidradopropionate (yield 67.8%). Ta.
ｂ、ｐ、５９ 〜６２ ℃／ ０ 、 ５ ｍ＋ｍｌ１
ｇｔＢ考考物
濃硫酸２９７ｇに発煙硝酸（ｄｌ ５２）２９７ｇを、
−５〜−１０℃に冷却下、４０分間で滴下し、更に同温
度に保ちつつ、３−ヒドロキシプロピ４ン酸エチルエス
テル［Ｊ、Ｏｒｇ。b, p, 59-62℃/0, 5 m+ml1
gtB Consideration: Add 297 g of fuming nitric acid (DL 52) to 297 g of concentrated sulfuric acid,
While cooling to -5 to -10°C, it was added dropwise over 40 minutes, and while maintaining the same temperature, 3-hydroxypropyl tetraphosphate ethyl ester [J, Org.
Ｃｈｅｍ、１３，７４９ （１９４８）に記載の方法で
合成した。］ ２７９ｇを３０分間で適正した。０℃で
２時間攪拌したのち、２．５ｋｇの氷にあけ、エーテル
１」を加えて抽出した。エーテル層を水、飽和型ソウ水
、飽和食塩水で順次洗浄し、無水硫酸ナトリウムで乾燥
し、溶媒を留去後蒸留し、３−ニドラドプロピオン酸エ
チルエステル３５８ｇ （収率８２％）を得た。It was synthesized by the method described in Chem, 13, 749 (1948). ] 279g was prepared in 30 minutes. After stirring at 0°C for 2 hours, the mixture was poured into 2.5 kg of ice, and extracted with ether 1''. The ether layer was washed successively with water, saturated sodium chloride water, and saturated brine, dried over anhydrous sodium sulfate, and distilled after distilling off the solvent to obtain 358 g (yield: 82%) of ethyl 3-nidoradopropionate. Ta.
ｂ、９．６４〜ｂ
実施例１
水素化ホウ素ナトリウム４１ｇと無水環化カルシウム６
１ｇをジメトキシエタン６００１に加えて懸濁させた。b, 9.64-b Example 1 41 g of sodium borohydride and 6 anhydrous cyclized calcium
1 g was added to dimethoxyethane 6001 and suspended.
これに攪拌下、３５〜４０℃で３−ニドラドプロピオン
酸エチルエステル１６３ｇを約３０分間で滴下し、同温
度に保ちつつ１時間ｌｊｉ！拝したのち、室温に戻し、
２０時間攪拌した。163 g of 3-nidradopropionic acid ethyl ester was added dropwise to this at 35 to 40°C with stirring over about 30 minutes, and the temperature was maintained at the same temperature for 1 hour. After worshiping, return to room temperature,
Stirred for 20 hours.
これにエーテル５００真！を加え、更に水冷下に水１６
ｇ＋ｍｌを滴下しｔこのち、水浴をはずし、３０分間攪
拌しｔ二。これを減圧ろ過し、不溶物を５００ｍ１のエ
ーテルで洗浄し、洗液とる液とを合わせ、無水硫酸ナト
リウムで乾燥した。溶媒を留去後蒸留し、３−ニドラド
プロパノールｘｏ９．ｓｇ（収率８２７％）を得た。Ether 500 true on this! Add 16 ml of water and cool with water.
After that, remove the water bath and stir for 30 minutes. This was filtered under reduced pressure, the insoluble matter was washed with 500 ml of ether, the washing liquid was combined with the washing liquid, and the mixture was dried over anhydrous sodium sulfate. After removing the solvent, distillation was performed to obtain 3-nidradopropanolxo9. sg (yield 827%) was obtained.
ｂ、ｐ、５５〜５６℃／ ０ 、１５ ＋ｉ＋ａｌ１ｇ
実施例２
水素化ホウ素ナトリウム１４．２ｇと無水塩化マグネシ
ウム１７９ｇをジメトキシエタン２２０＋ｍｌに加えて
懸濁させた。これにｔｌ！Ｐｌ！下３５〜４０℃で３−
ニドラドプロピオン酸エチルエステル７５ｇを約３０分
間で滴下したのち、室温に戻し２０時ｔｏ＋攪梓したの
ち、エーテル２００１を加え、水７５纏１を滴下した。b, p, 55-56℃/0, 15 +i+al1g
Example 2 14.2 g of sodium borohydride and 179 g of anhydrous magnesium chloride were added to 220+ml of dimethoxyethane and suspended. TL for this! Pl! 3- at lower 35-40℃
After dropping 75 g of nidradopropionate ethyl ester over about 30 minutes, the mixture was returned to room temperature and stirred at 20:00, after which ether 2001 was added and 75 g of water was added dropwise.
これを室温で３０分Ｉｊｌｌ！ｌ、たのち、減圧ろ過し
、不溶物を２００ｍ１のニー、チルで洗浄し、洗液とる
液とを合わせ、無水硫酸ナトリウムで乾燥した。溶媒を
留去後蒸留し、３−ニドラドプロパノール４７．３ｇ（
収率７８％）を得た。Let this sit at room temperature for 30 minutes! After filtration under reduced pressure, the insoluble matter was washed with 200 ml of Ni-chill, and the washing liquid and the liquid were combined and dried over anhydrous sodium sulfate. After the solvent was distilled off, 47.3 g of 3-nidradopropanol (
A yield of 78%) was obtained.
ｂ、ｐ、ｓｓ 〜 ５６ ℃／ ０ １５ 飄醜Ｈｇ実
施例３
３−ニドラドプロピオン酸エチルエステル１９２ｇをト
ルエン１６Ｑａ＋１に溶かし、−１５〜−１０℃に冷却
下７０％ジヒドロ−ビス（２−メトキシエトキシ）アル
ミン酸ナトリウム／トルエン３７５ｇを滴下し、更に同
温度下に２時間攪拌後、６Ｎ−塩酸２８０１を加え、ろ
過した。ろ液を６０ｍ１の水で洗浄後、無水硫酸ナトリ
ウムで乾燥し、溶媒を留去後蒸留し、３−ニドラドプロ
パツール６８．５ｇ（収率４８．１％）を得た。b, p, ss ~ 56 °C / 0 15 Ugly Hg Example 3 192 g of 3-nidradopropionic acid ethyl ester was dissolved in toluene 16Qa+1, and while cooling to -15 to -10 °C, 70% dihydro-bis(2-methoxy 375 g of sodium ethoxyaluminate/toluene was added dropwise, and after further stirring at the same temperature for 2 hours, 6N hydrochloric acid 2801 was added and filtered. The filtrate was washed with 60 ml of water, dried over anhydrous sodium sulfate, the solvent was distilled off, and then distilled to obtain 68.5 g (yield: 48.1%) of 3-nidradopropatol.
ｂ、ｐ、ｓｓ〜５６℃／ ０ 、１５ ｍｍＨｇ特許出
願人 大正製薬株式会社
代理人 弁理士 北 川 富 造b, p, ss ~ 56℃/0, 15 mmHg Patent applicant Taisho Pharmaceutical Co., Ltd. Representative Patent attorney Tomizo Kitagawa
Claims (1)
アルキルエステルを水素化ホウ素系または水素化アルミ
ニウム系還元剤を用いて還元する３−ニドラドプロパノ
ールの製造法。(1) A method for producing 3-nidoradopropanol, which comprises reducing 3-nidoradopropionic acid lower alkyl ester using a borohydride-based or aluminum hydride-based reducing agent in an inert solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59033247A JPS60178845A (en) | 1984-02-23 | 1984-02-23 | Production of 3-nitratopropanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59033247A JPS60178845A (en) | 1984-02-23 | 1984-02-23 | Production of 3-nitratopropanol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60178845A true JPS60178845A (en) | 1985-09-12 |
| JPH0320381B2 JPH0320381B2 (en) | 1991-03-19 |
Family
ID=12381147
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59033247A Granted JPS60178845A (en) | 1984-02-23 | 1984-02-23 | Production of 3-nitratopropanol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60178845A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013513577A (en) * | 2009-12-11 | 2013-04-22 | ディーエスエム アイピー アセッツ ビー．ブイ． | Nitrooxyalkanoic acid and its derivatives in feed to reduce ruminant methane emissions and / or improve ruminant performance |
| CN111592460A (en) * | 2020-06-18 | 2020-08-28 | 南通华康医药科技有限公司 | Preparation method of 3-hydroxy propionate |
-
1984
- 1984-02-23 JP JP59033247A patent/JPS60178845A/en active Granted
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013513577A (en) * | 2009-12-11 | 2013-04-22 | ディーエスエム アイピー アセッツ ビー．ブイ． | Nitrooxyalkanoic acid and its derivatives in feed to reduce ruminant methane emissions and / or improve ruminant performance |
| US9365489B2 (en) | 2009-12-11 | 2016-06-14 | Dsm Ip Assets B.V. | Nitrooxy alkanoic acids and derivatives thereof in feed for reducing methane emission in ruminants, and/or to improve ruminant performance |
| CN111592460A (en) * | 2020-06-18 | 2020-08-28 | 南通华康医药科技有限公司 | Preparation method of 3-hydroxy propionate |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0320381B2 (en) | 1991-03-19 |
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