DE1493619A1 - Process for the preparation of 3- (3 ', 4'-dihydroxyphenyl) -2-methylalanine - Google Patents

Description

Re: patent application P 14 93 619.7

Note: Egyeaält Gy & gyszer- es Tapszergy & r, Budapest

Process for the preparation of 3- (3 '«4 * -dihydroxyphenyl) - 2-methy! Alanine

Since ₈ 3- (3 ', 4'-dihydroxyphenyl) -2.methylalanine and one derivative aoylated on the hydroxyl groups or on the nitrogen atom are known to have an advantageous antihypertensive effect or by splitting off τοη aoyl groups in .ig.nd . UrhlMAwn to be transferred. I am experienced

d _{i #} . _tr connections was · τοη β.Α. Stein und Hit -... oferi.Un UA.0he «.8oc. 22, 700, 1955), after wtlohe. ditwirT ^ iÄd «« · «au. 3.4- »l« .thexT. _p henylac.ton via HydmJitelMtriW · _Λ . iwl.ehenproduct. her _f . »t * llt to be. Am HohUil ii "_#e Terfahren. iet the extraordinary long. As the synthesis takes place, the hydantoin is broken down. ring ·, .tw · 70 hours. The .iMz.ln.n steps of the Synthe.e Im crefem Ulvmin * d * raw «tftth * t, that egg product can

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only difficult and with considerable loss of sound the big one Quantities of the inorganic by-products isolated and purified will. The starting material used was 3,4-Dlsmthosy-phenylaoeton can only with very poor yields clay 45 - 50 j < getting produced"

It has now been found that 3- (3 ⁽ .4 -'-Dihydroxyphtnyl) -2- ■ ethylalanine of the general formula

It can be produced much more simply and advantageously if diazotized 4-amino-veratrole is used, advantageously in the Siotierungttedium in the presence of copper (II) chloride with an aqueous or aqueous-organic, advantageously aqueous acetone solution of methyl methacrylate and the thus obtained 3— (3 *, 4 ^f -Dimothoxyphenyl) -2-chloro-2-ethyl-propionic acid-ethyl-eeter hydrolyzed in the same Reaktlonsmediua and in a known manner, with liquid Ammo

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niak aminated and as "receive" 5- (3 ^f »Biastaoiy 4'-phenyl) -2- ■ ethylalanin in a known manner aioh dsaethyliert} erhsV the tene Prouukt can then optionally an inorganic or old organieohen acid into the corresponding addition hall converted to .

The method according to the invention is not only significantly simpler than the previously known production methods of this Compound, but also has the further advantage that the end product is obtained in much greater purity, which is also obtained directly from the better sonic points dee raw product. The connection established according to the invention of the general formula I can be converted into therapeutically applicable salts according to methods known per se or inorganic acid.

The implementation of the process according to the invention is through the next example explained in more detail; the invention is but in no way limited to this example.

example
15 »3 R 4-Aminoveratrol are concentrated in 30 ml. SaI * -

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Saur dissolved "and 40 uX water and at a Teaperatw" wisohen 0 to -5 ⁰ C, "it an aqueous solution of 8 g ron latriuanitrit diasotiert" She is DiaBoniuelttsung Bit 12 g of crystalline copper (II) -ohlorid versetet, then ei is " · Dissolve 30 g of methyl aethaorylate in 90 ml of aoeton dropwise sugeset, and the ice cream is stirred for β hours at Siaa temperature. Excess acetone and methacrylate are generally distilled off, and the solution is diluted with water and extracted with chloroform. The chlorofora solution is freed from the acid by washing with water, then dried, and the chlorofora is distilled off; As a residue, 20 g of crude methyl 3- (3 'A ' -dirnethoxyphenyl) -2-chloro-2-methyl-propionic acid are obtained in a dark oily product. Yield 73.5 ϊ ι • The product can b below 0.3 Torr "i be distilled 136 ⁰ C.

An amount of this oily raw material equivalent to 6 g of pure Beter Products are aged in a mixture of 40 ml. 85 pounds of formic acid and 20 ml of concentrated hydrochloric acid a * water bath 2 hours hydrolyzed. The mixture is then diluted with 200 μl of water and extracted with chloroform. The combined chloroform extract is extracted with 5% sodium hydroxide solution, and the resulting alkaline solution is acidified while cooling. Bs

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is obtained in light brown, raw, solidified oil. DIt Men «· de · Product · 1st 4 g (71 f d. Th.), F. 64 - 87 ⁰ O.

The thus obtained 3- (3 _'4'-t Dlmethoat3rph "nyl) -2-ohlor-2 -'» ethylpropioneäure is umgesetst 10 hours in a "bomb -geschlossenen" tube at 50 ⁰ O flSigem with ammonia. After distilling off the ammonia, the product obtained is dissolved in water and acidified with sodium acid. Ss is "it nahesu quantitative yield 3- (3 ', 4 ^f -Dimethoxyphenyl) -2 ~« · thy1-alanine hydroohlorid obtained, melting after recrystallization au · water at 287 ⁰ C "

By DesalkyHeren this product with bromine alcoholic acid 3- (3 * »4 ¹ -Dihydroxyphenyl) -2-methyl-alanine is obtained, P. 313 - 314 ⁰ C.

- claim -

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Claims (1)

Patents a ρ ru ο h Process for the production of 3- (31 ₁ 4 »-dihydroxyphenyl) -2- fflethylalanine of the general formula I. OH, CH ₂ - C - COOH H \ characterized in that one diaeotiertee 4- / minoveratrol advantageously la Dlasotierungsmediuin in the presence of copper (II) chloride alt an aqueous or aqueous-organic, advantageously aqueous-acetone solution of methyl methacrylate umeetit and the thus formed 3- (3 'i4' -DimethoXyphenyl) -2 * 2-chloro-m # thyl-propion3äureester in the same Heaktionaneditui hydrolyzed and else, aminated in a known "/ m & expedient Blg old liquid Anisoniak and the resulting 3- (3 _'f 4 Diiiethoxyphenyl) -2- "Ethylalanine is deaethylated in a manner known per se and the product obtained is converted, if appropriate, with an inorganic or organic acid into the corresponding addition al". 90982A / 1239