CS267785B1

CS267785B1 - Alkyl esters of 4-C-3-halo-2-hydroxy-pro-alkoxy-phenylcarbonic acid and the methods for their preparation

Info

Publication number: CS267785B1
Application number: CS883418A
Authority: CS
Inventors: Jozef Rndr Csc Csollei; Alois Doc Rndr Phmr Borovansky; Ludek Doc Rndr Drsc Benes
Original assignee: Csoellei Jozef; Borovansky Alois; Benes Ludek
Priority date: 1988-05-20
Filing date: 1988-05-20
Publication date: 1990-02-12
Also published as: CS341888A1

Abstract

Riešenie sa týká alkylesterov 4-C/3- -halogén-2-hydroxy/-propoxy3 fenylkarbanové; kyseliny všeobecného vzorca i, v ktoron R je priamy alkyl s 1 až 5 atóraami uhlíka, rozvětvený alkyl s 3 až 4 atónani uhlika, alkenyl s 2 až 3 atómarni uhlíka, cykloalkyl s 5 až 7 atómarni uhlika a X je halogén. Uvedené zlúčeniny je možně připravit tak, že sa nechá reagovat alkylester kyseliny 4-hydroxyfenytkartamovej s 3-halogén-1,2-epoxypropénom za bázickej katalýzy piperidinu du- . sikatých zlúčenin alebo alkylester kyseliny 4-[72,3-epoxy/-propoxyJ fenylkarbamovej s kyselinou halogěnvodikovou vo vodnom roztoku etylmetylketónu alebo acetonu. Riešenie spadá do odboru organických syntéz.The solution relates to 4-C/3-halo-2-hydroxy/-propoxy-3-phenylcarbanoic alkyl esters; acids of general formula i, where R is straight alkyl with 1 to 5 carbon atoms, branched alkyl with 3 to 4 carbon atoms, alkenyl with 2 to 3 carbon atoms, cycloalkyl with 5 to 7 carbon atoms and X is halogen. The mentioned compounds can be prepared by allowing the alkyl ester of 4-hydroxyphenytocartamic acid to react with 3-halo-1,2-epoxypropene under the basic catalysis of piperidine du-. of the following compounds or 4-[72,3-epoxy/-propoxyJ-phenylcarbamic acid alkyl ester with hydrohalic acid in an aqueous solution of ethyl methyl ketone or acetone. The solution falls into the field of organic synthesis.

Description

EN 267 785 B1 1

BACKGROUND OF THE INVENTION The present invention relates to the alkyl esters of 4- (3-chloro-2-hydroxy) phenylpyrrolidine of the general formula (I).

(I) wherein R is alkyl of 1 to 5 carbon atoms, branched alkyl of 3 to 4 carbon atoms, alkenyl of 2 to 3 carbon atoms, cycloalkyl of 5 to 7 carbon atoms, X is halogen , as a method of producing these substances.

The compounds of the invention have not been described in the literature. May be used to prepare substances with locally anesthetic, anti arrhythmic, beta adrenolytic and spasmolytic activity.

The compounds of formula (I) may be prepared according to the invention by two methods. in the case of 4-hydroxy-phenylcarbamic acid alkyl ester of general formula II is reacted

Wherein R is as defined above with 3-halo-1,2-epoxypropane under basic piperidine catalysis, preferably in an aqueous bath for 10 hours. Compounds of formula (II) may be prepared, for example, as described in Chabrier, F. et al., Bull. Soc. Chin. Fr., 1353 (1955).

In the second instance, the alkyl ester of 4-C, 2,3-epoxy / propoxy J-carbocarboxylic acid of general formula (III) is reacted.

wherein R is as defined above, with logenic acid in an aqueous solution of ethyl methyl ketone or acetone. It was found to be advantageous to carry out the reaction with 48% hydrobromic acid in aqueous acetone at room temperature for 4 hours. The production process is the same as that described by ZBls et al .: Λrzneim.-Forsch, 2, 233 (1983). The compounds of the general formula III can be prepared by the MS. AO 266234, Oalium starting compounds are commercially available and available from the literature known as [beta] -inophenol, chloroformic esters, 3-halo-1,2-epoxypropane.

These examples illustrate, but do not limit, the invention. Example 1

The reaction mixture of 19.3 g (0.1 mol) of 4-hydroxyphenylcarbamic acid allyl ester, 20.6 g (0.15 mol) of 1-bromo-2,3-epoxypropane and 1 ml of piperidine was heated on water for 10 h. After the reaction is complete, the bromohydrin is distilled off under vacuum and the residue is dissolved in chloroform. The organic phase is shaken with 10% hydrochloric acid and then with water and dried over anhydrous magnesium sulphate, the chloroform is distilled off under low vacuum. white crystalline solid, mp 73 ° C, 74 ° C, yielded 71 X theory. Example 2 15.9 g (0.06 mol) of 4-f, 2,3-epoxy-propoxyphenylcarbamic acid butyl ester are dissolved in 200 ml of acetone and 52 ml of water and 40 ml of 48 X acid are added sequentially at room temperature. hydrobromic acid. After 4 hours of the reaction mixture, the crystals formed were filtered off with suction and washed with aqueous acetone. The resulting 4-C 3-bromo-2-hydroxy-propoxy-phenylcarbamic acid butyl ester was recrystallized from ethanol, mp 99-10 ° C. Yield: 68% of theory. Using the methods described above, the following compounds have been prepared in the literature: 1 / 4- [73-Bromo-hydroxy-propoxy-phenylcarbamic acid methyl ester] of Example 1 and 2 / mp 70-72 ° C / diluted ethanol /

Elem. anal. for C ^ HH ^ HON ^O vypOrnd: C, 43.43 / 43.63; H 4.63 / 5.00; H 4.60 / 4.47; 2/4-C 3-Bromo-2-hydroxy-propoxy-phenylcarbamic acid ethyl ester (Example 1 and 2) m.p. 98-100 ° C / methanol /

Elem. anal. for C12H16N045r, calc .: C 45.29 / 45.11; H 5.06 / 5.33; N, 4.40 / 4.52; 3 / 4- [3-Bromo-2-hydroxy / propoxy] phenylcarbamic acid propyl ester (Example 1 and 2) mp 103-104 ° C / ethanol /

Elem. anal. for C ^ HH ^ NONO BrBr./n .: C 47.00 / 47.23; H, 5.46 / 5.51; 4.21 / 4.16; 4/4 - [(3-Bromo-2-hydroxy) -propoxy! phenylcarbamic acid (Example 1 and 2) rt 88-90 ° C / diluted ethanol /

Elem. anal. for C ^ HH ^ NONO BrBr./n .: C 47.00 / 46.78; H, 5.46 / 5.55; N 4.21 / 4.16; 5/4-tert-Bromo-2-hydroxy-propoxy-phenylcarbamic acid butyl ester (Example 1 and 2) mp 99-100 ° C / ethanol /

Elem. anal. for C ^ HH ^ NON ^OrRrN: C, 48.56 / 43.44; K 5.82 / 5.72; N4, C4 / 3.74; C5 267 785 31 3 6 / [3-Bromo-2-hydroxy / propoxy] female phenylacetate; (Stage 1 and 2) - with an aqueous solution of ethyl methyl ketone (m.p. 97-98 ° C / ethanol set up)

Eten, anat, for C ^ HH ^ gNONOBr .Or: C 48.56 / 48.44; H, 5.82 / 5.96; N, 4.04 / 4.09; 7/4 - [(3-Bromo-2-hydroxy) propanoyl] phenylcarbamic acid pentyl ester (Example 1)? 2 - with an aqueous solution of ethyl methyl ketone (mp 92-93 ° C / diluted with ethanol / silica). anal. for C ^ HH ^ NONO BrBr./N .: C 50.00 / 50.27; H, 6.15 / 6.21; n 3.38 / 3.79; 8/4 - [(3-Bromo-2-hydroxy) -propoxy] phenylcarbamic acid cyclohexyl ester / stage 1 and 2 / mp 105-107 ° C / ethanol /

Elcm. Anal, C ^ ^H ^ NON ^O vypS.R. Ex .: C 51.62 / 51.51; H, 5.95 / 5.73; N 3,76 / 4,011 9/4 - [(3-Bromo-2-hydroxy) -propoxy] phenylcarbamic acid allyl ester according to Examples 1 and 2 / T. T. 73 3? 74 ° c / diluted methanol /

Stem. anal. for C ^ H ^ NO ^ r off / May; C 47.28 / 47.12; B 4.88 / 5.06; H 4.24 / 4.18;

The invention can be found to be useful in organic healing, in pharmaceuticals ii, l and r-macotics and media.

Claims

EN 267 785 B1 P R E B T I T OF THE INVENTION

1. Alkyl esters of A-C 3 -halogen-2-hydroxy / propoxy] phenylcarbamate of general formula I01! Where R is a alkyl group having from 1 to 5 carbon atoms, branched alkyl having from 3 to 4 carbon atoms, alkenyl having from 2 to 3 carbon atoms, cycloalkyl having from 5 to 7 carbon atoms, and X is halogen.

2. Processes for producing alkyl esters according to claim 1, wherein a compound of formula II is reacted with OH

(II), NHCOOR wherein R is as defined above with a 3-h and logene-1,2-epoxide petroleum, under the basic catalysis of r1d1 nu.

3. The process for producing alkyl esters according to item 1 is characterized by! by reacting a compound of formula III

wherein R is as defined above with halo hydrocarbon in an aqueous solution of ethyl methyl ketone or acetone.