CH415587A - Process for the preparation of N-alkyl-substituted 3-methoxy-4-carbamidomethoxyphenylacetic acid alkyl and alkenyl esters - Google Patents

Description

  

  



   Process for the preparation of N-alkyl-substituted 3-methoxy-4-car. alkyl and alkenyl esters of bamidomethoxyphenylacetic acid
It has been found that N-alkylated 3-methoxy4-carbamidomethoxyphenyl acetic acid alkyl and alkenyl esters are surprisingly short-acting narcotics which can be used intravenously and which, compared with the barbituric acid derivatives, which have hitherto been exclusively used for this purpose, differ in animal experiments due to a very rapid decrease in activity and the absence of the so-called Mark ¸overhang¯.



   According to the invention, these compounds are prepared by esterifying corresponding N-alkyl-substituted 3-methoxy-4-carbamidomethoxyphenylacetic acids with saturated or unsaturated aliphatic alcohols or lower N-alkyl-substituted 3-methoxy-4-carbamidomethoxyphenylacetic acid alkyl esters, such as. B. the methyl ester, converted into the corresponding higher esters by transesterification with higher alcohols.



   The 3-methoxy-4-N, N-diethylcarbamidomethoxyphenylacetic acid-n-propyl ester obtainable by the process according to the invention was compared with the known 5-methyl-5-cyclohexenyl-N-methyl-barbituric acid sodium. The following results were obtained in the dog when administered intravenously:
Process comparison product product a) dose 40 mg / kg 40 mg / kg: g b) anesthesia grade 8 VI VI c) total anesthetic time 17 min. 166 min.

      d) anesthetic time from
VI-IV in% of the total anesthetic time * 47% 17%
The results for rabbits are the same
It was accordingly found that with the same dosage, the product obtained by the method according to the invention allows the same depth of anesthesia to be achieved as the comparison product, but with a significantly shorter total anesthetic duration.



  (The total duration of anesthesia is understood to mean the time from the onset of anesthesia to the disappearance of any narcotic symptoms, i.e. up to the point in time at which the animal behaves completely normally again. Transferred to humans, this point in time provides an indication of roadworthiness of the anesthetized individual).



   As a result, the product obtainable according to the invention leads to a considerably faster roadworthiness than the comparative product, an advantage which is of decisive importance especially in minor surgery, where only very short anesthetic times are required. Apart from the comparative product, no such short anesthetic times - when the full tolerance stage has been reached - have become known for the other introduced narcotics to be used intravenously.



   example 1
50 g of 3-methoxy-4-N, N-diethylcarbamidomethoxyphenyl acetic acid methyl ester are dissolved in 300 ml of n-propanol and, after the addition of 0.1 g of sodium n-propoxide, an anesthetic stage VI corresponds to Magnus-Girndt deep anesthesia with complete lack of reflexes; Stage IV anesthesia corresponds to the lateral position with the corneal and pincer intact
Reflex. The time from anesthesia stage VI to IV is roughly a measure of the time available for surgical interventions. seed column heated until no more methanol passes over. After driving off the excess propyl alcohol, the mixture is distilled in vacuo and 46 g of des is obtained
3-Methoxy-4-N, N-diethylcarbamidomethoxyphenylacetic acid n-propyl ester of bp 0.7 210-212¯.



   Example 2
20 g of 3-methoxy-4-N, N-carbamidomethoxyphenylacetic acid (melting point 119-120), which can be obtained from the methyl ester by saponification with alkali, is refluxed with 200 ml of m-propyl alcohol containing 3% hydrogen chloride for 8 hours . After the solvent has been driven off, it is taken up in benzene, washed with sodium carbonate solution and water and dried with sodium sulfate. After driving off the benzene, the residue is distilled in vacuo and 19.8 g are obtained
3-Methoxy-4-N, N-diethylcarbamido methoxyphenyl acetic acid n-propyl ester of boiling point 0.7 210-212¯.



   Example 3
50 g of 3-methoxy-4-N, N-diÏ'thylcarbanudo methoxyphenylessigsäuremlethylester are dissolved in 300 ml of allyl alcohol and, after the addition of 0.1 g of sodium, heated in an intensive cooler until no more methano passes over. After the excess allyl alcohol has been removed, the product is distilled under vacuum and 43 g are obtained
3-Methoxy-4-N, N-diethylcarbamido-methoxy-phenylacetic acid allyl ester of bp. O.8208-210.

 

Claims (1)

PATENT CLAIM Process for the preparation of N-alkyl-substituted 3-methoxy-4-carbamidomethoxyphenylacetic acid alkyl and alkenyl esters, characterized in that N-alkyl-substituted 3-methoxy-4-carbamido methoxyphenylacetic acids with saturated or unsaturated. aliphatic alcohols esterified or N-alkyl-substituted 3-methoxycarbamidomethoxyphenyl acetic acid methyl or ethyl ester transesterified with alcohols with more than 2 carbon atoms. SUBClaim 1. The method according to claim, characterized in that the methyl ester is esterified with a saturated or unsaturated monohydric alcohol.