CS277262B6 - Process for preparing hydrochloride of 1-amino-1-cyclopentanecarboxylic acid methyl ester - Google Patents
Process for preparing hydrochloride of 1-amino-1-cyclopentanecarboxylic acid methyl ester Download PDFInfo
- Publication number
- CS277262B6 CS277262B6 CS905132A CS513290A CS277262B6 CS 277262 B6 CS277262 B6 CS 277262B6 CS 905132 A CS905132 A CS 905132A CS 513290 A CS513290 A CS 513290A CS 277262 B6 CS277262 B6 CS 277262B6
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- amino
- cyclopentanecarboxylic acid
- methyl ester
- acid methyl
- toluene
- Prior art date
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- VLNNACMZTDZCFH-UHFFFAOYSA-N methyl 1-aminocyclopentane-1-carboxylate Chemical compound COC(=O)C1(N)CCCC1 VLNNACMZTDZCFH-UHFFFAOYSA-N 0.000 title 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- 239000011541 reaction mixture Substances 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- NILQLFBWTXNUOE-UHFFFAOYSA-N 1-aminocyclopentanecarboxylic acid Chemical compound OC(=O)C1(N)CCCC1 NILQLFBWTXNUOE-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 3
- 230000032050 esterification Effects 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- OPUJUITUYWGUEP-UHFFFAOYSA-N methyl 1-aminocyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1(N)CCCC1 OPUJUITUYWGUEP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- 150000004702 methyl esters Chemical class 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 2
- ONNMHNDIUIHULO-UHFFFAOYSA-N 1-aminocyclopentane-1-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1(N)CCCC1 ONNMHNDIUIHULO-UHFFFAOYSA-N 0.000 abstract 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 238000001816 cooling Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 241001156002 Anthonomus pomorum Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- NLLGKNYQDQBMFW-UHFFFAOYSA-N ethyl 1-aminocyclopentane-1-carboxylate Chemical compound CCOC(=O)C1(N)CCCC1 NLLGKNYQDQBMFW-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Způsob výroby hydrochloridu methylesteru kyseliny l-amino-l-cyklopentankarboxylové esterifikací kyseliny methanolem, nasyceným chlorovodíkem. Postup se vyznačuje tím, že při dvojím zahuštování reakční směsi se užívá přídavek toluenu, tím se výhodně odstraňuje voda z reakce a posouvá se rovnováha. Produkt, hydrochlorid methylesteru kyseliny 1-amino-l-cyklopentankarboxylové slouží jako meziprodukt syntézy léčiv.Process for preparing methyl ester hydrochloride 1-amino-1-cyclopentanecarboxylic acid by esterifying the acid with methanol, saturated with hydrogen chloride. The procedure is characterized in that in the double concentration of the reaction mixture it uses the addition of toluene, thereby preferably being removed water from the reaction and shifts the balance. Product, methyl ester hydrochloride 1-amino-1-cyclopentanecarboxylic acid serves as an intermediate in drug synthesis.
Description
Vynález se týká způsobu výroby hydrochloridu methylesteru kyseliny 1-amino-l-cyklopentankarboxylové o vzorci IThe invention relates to a process for the preparation of 1-amino-1-cyclopentanecarboxylic acid methyl ester hydrochloride of formula I
(I) z kyseliny 1-amino-l-cyklopentankarboxylové.(I) from 1-amino-1-cyclopentanecarboxylic acid.
Methyl nebo ethylestery kyseliny 1-amino-l-cyklopentankarboxylové jsou známy. Připravují se esterifikací podle K. Fischera (Chem. Ber. 39., 2893 (1906)), kdy se asi desetinásobný přebytek alkoholu, nasycený chlorovodíkem, po několikahodinovém varu odpařuje a proces s varem a odpařením se opakuje, ještě jednou. Podobná metodika byla užita i pro přípravu ethylesteru kyseliny 1-amino-l-cyklopentankarboxylové (Arch. Pharm. 1981 314 (1) 44).1-Amino-1-cyclopentanecarboxylic acid methyl or ethyl esters are known. They are prepared by esterification according to K. Fischer (Chem. Ber. 39, 2893 (1906)), in which a ten-fold excess of alcohol saturated with hydrogen chloride is evaporated after boiling for several hours and the boiling and evaporation process is repeated once more. A similar methodology was used to prepare 1-amino-1-cyclopentanecarboxylic acid ethyl ester (Arch. Pharm. 1981 314 (1) 44).
Příprava methylesterů kyselin pomocí methanolu a thionylchloridu za teplot pod 0 °C podle Brennera (Helv. Chim. Acta 36 1109 (1953)) je vzhledem k surovinám, podmínkám a ekologickým hlediskům pro výrobní technologii málo vhodná.The preparation of methyl esters of acids with methanol and thionyl chloride at temperatures below 0 ° C according to Brenner (Helv. Chim. Acta 36 1109 (1953)) is not very suitable for the production technology due to the raw materials, conditions and ecological aspects.
Základním požadavkem při esterifikací alkoholýzou je posun rovnováhy reakce odstraňováním vody. Dosud aplikované metody dvojího odpaření při přípravě methylesteru poskytují požadovaný produkt, avšak jeho kvalita není prvotřídní, obsah esteru bývá maximálně do 95 hmot. %. ·The basic requirement for esterification by alcoholysis is to shift the equilibrium of the reaction by removing water. The double evaporation methods applied so far in the preparation of the methyl ester provide the desired product, but its quality is not first-class, the ester content is usually up to 95 wt. %. ·
Nevýhody dosud popsaných postupů odstraňuje způsob výroby podle vynálezu, který se vyznačuje tím, že se do reakční směsi přidává toluen v množství 50 až 150 hmot. % na hmotnost výchozí kyseliny 1-amino-l-cyklopentankarboxylové a po oddestilování rozpouštědel se operace jednou opakují. Po druhém zahuštění se suspenze krystalů produktu rozmíchá s etylacetátem a produkt se izoluj e.The disadvantages of the processes described so far are eliminated by the process according to the invention, which is characterized in that toluene is added to the reaction mixture in an amount of 50 to 150% by weight. % by weight of the starting 1-amino-1-cyclopentanecarboxylic acid and, after distilling off the solvents, the operations are repeated once. After a second concentration, the product crystal suspension is stirred with ethyl acetate and the product is isolated.
Toluen tvoří azeotrop s vodou, její odstranění je proto důkladnější a rovnováha je posunuta prakticky na stranu esteru. Podle nového postupu má ester obsah vyšší než 98 hmot. %. a obsah vody je nižší než 0,1 hmot. %.Toluene forms an azeotrope with water, so its removal is more thorough and the equilibrium is shifted practically to the ester side. According to the new process, the ester has a content of more than 98 wt. %. and the water content is less than 0.1 wt. %.
Hlavní předností postupu podle vynálezu je získání vysoce kvalitního produktu. Nejsou nutné čistící operace (například krystalizacemi za užití etheru).The main advantage of the process according to the invention is to obtain a high quality product. No purification operations are required (for example by crystallizations using ether).
Bližší podrobnosti postupu podle vynálezu vyplývají z následujícího příkladu, který tento postup pouze ilustruje, ale nijak neomezuje.Further details of the process according to the invention follow from the following example, which merely illustrates but does not limit this process.
PříkladExample
V reaktoru se míchalo 2,5 h 20 litrů methanolu nasyceného 1,6 kg chlorovodíku se 4,5 kg kyseliny 1-amino-l-cyklopentankarboxylové za refluxování reakční směsi. Po ochlazení se přidaly 4 litry toluenu a za vakua se zahušťovalo. Po získání 5 litrů kondenzátu se přidalo 2,3 litru toluenu a zahušťovalo se do vzniku husté kaše.The reactor was stirred for 2.5 hours with 20 liters of methanol saturated with 1.6 kg of hydrogen chloride with 4.5 kg of 1-amino-1-cyclopentanecarboxylic acid while refluxing the reaction mixture. After cooling, 4 liters of toluene were added and concentrated in vacuo. After obtaining 5 liters of condensate, 2.3 liters of toluene was added and concentrated to a thick slurry.
Přidalo se 20 litrů methanolu nasyceného 0,8 kg chlorovodíku a míchalo se za refluxu 1 h. Po ochlazení se přidalo 1,6 litru toluenu a zahušťovalo se obdobně jako shora s přídavkem 1,5 litru toluenu.20 liters of methanol saturated with 0.8 kg of hydrogen chloride were added and stirred at reflux for 1 hour. After cooling, 1.6 liters of toluene were added and concentrated in the same manner as above with the addition of 1.5 liters of toluene.
Hustá kaše krystalů byla rozmíchána s 13 litry etylacetátu, po ochlazení se filtrovalo, promývalo a sušilo.The thick slurry of crystals was stirred with 13 liters of ethyl acetate, after cooling, filtered, washed and dried.
Byl získán hydrochlorid methylesteru kyseliny 1-amino-l-cyklopentankarboxylové s výtěžkem 90 % teorie. Obsah byl více než 98 hmot. %, obsah vody 0,05 hmot. %.1-Amino-1-cyclopentanecarboxylic acid methyl ester hydrochloride was obtained in a yield of 90% of theory. The content was more than 98 wt. %, water content 0.05 wt. %.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS905132A CS277262B6 (en) | 1990-10-22 | 1990-10-22 | Process for preparing hydrochloride of 1-amino-1-cyclopentanecarboxylic acid methyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS905132A CS277262B6 (en) | 1990-10-22 | 1990-10-22 | Process for preparing hydrochloride of 1-amino-1-cyclopentanecarboxylic acid methyl ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS513290A3 CS513290A3 (en) | 1992-05-13 |
| CS277262B6 true CS277262B6 (en) | 1992-12-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS905132A CS277262B6 (en) | 1990-10-22 | 1990-10-22 | Process for preparing hydrochloride of 1-amino-1-cyclopentanecarboxylic acid methyl ester |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS277262B6 (en) |
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1990
- 1990-10-22 CS CS905132A patent/CS277262B6/en unknown
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| Publication number | Publication date |
|---|---|
| CS513290A3 (en) | 1992-05-13 |
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