CS239414B1

CS239414B1 - Process for preparing 1- [4-acetoxy-2,3,5-trimethylphenoxy] -3-isopropylamino-2-propanol

Info

Publication number: CS239414B1
Application number: CS84816A
Authority: CS
Inventors: Jozef Nevydal; Milan Manduch; Richard Frimm; Ondrej Gattnar
Original assignee: Jozef Nevydal; Milan Manduch; Richard Frimm; Ondrej Gattnar
Priority date: 1984-02-06
Filing date: 1984-02-06
Publication date: 1986-01-16
Also published as: CS81684A1

Abstract

SpOsob přípravy 1-(4-acetoxy-2,3,5- -trimetylfenoxy)-3-izopropylamino-2-propanolu vzorca OCOCH3 H3<Z CH3 ch3 ch3 O - cn2 - CHÍH - CH2 - NH— CH OH CH, Z z 1 -(4-acetoxy-2,3,5-trimetylfenoxy)-2,3- -epoxypropánu vzorca o-ch2- CH —CHj V a izopropylamínu, vyznačený tým, že reakcia sa uskutočňuje v izopropylamině, ktorý je súčasne rozpúšťadlo i reakčné komponenta pri tlaku 0,2 až 0,3 MPa a teplote 50 až 70 °C.A method for preparing 1-(4-acetoxy-2,3,5-trimethylphenoxy)-3-isopropylamino-2-propanol of the formula OCOCH3 H3<Z CH3 ch3 ch3 O - cn2 - CHÍH - CH2 - NH— CH OH CH, Z from 1-(4-acetoxy-2,3,5-trimethylphenoxy)-2,3- -epoxypropane of the formula o-ch2- CH —CHj V and isopropylamine, characterized in that the reaction is carried out in isopropylamine, which is both a solvent and a reaction component at a pressure of 0.2 to 0.3 MPa and a temperature of 50 to 70 °C.

Description

239414 2

The present invention relates to a process for the preparation of 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -3-isopropylamino-2-propanol of formula OCOCH 3

HoCr ^ SiCHa

UcH33, CH, (I)

OH 'CH, isopropylamine and 1- (4 / ap / oxo-2,3-trimethylphenoxy) -2,3-epoxypropane

CH - CH

In (II), a compound of formula I is obtained practically free of by-products, which is a pharmaceutical substance for the Trimepranol dosage form.

Podlá ča. 128471, the reaction of 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -2,3-epoxypropane with isopropylaine is carried out in water) of an aqueous alkanol of 1-3 carbon atoms or in the alkanol itself at atmospheric pressure. The disadvantage of this process is the formation of a by-product of 1- (4-hydroxy-2,3,5-trimethyl-phenoxy) -3-isopropylamino-2-propanol of formula

OH

HnCr ^ SiCH,

O-CH, - CH - CH, - NH - CH 1 CH, OH C 3, which is produced in an amount of 3 to 5% during the reaction itself by saponification of the acetate group This substance is an undesirable additive, its removal below the permissible level requires a minimum of twice as crystallization. A further disadvantage of the above-mentioned process is the thermal thermal stressing of the reaction mixture during the distillation of the solvent, resulting in a decrease in the quality and yield of the product. From an operational point of view, using a solvent and an excess of isopropylamine, it is necessary to regenerate the solvent-isopropylamine mixture by rectification, which is laborious and energy-intensive.

The above drawbacks are overcome by the method of the invention, which consists in preparing 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -3-isopropylamino-2-propanol (I) from 1- (4-acetoxy-2) , 3,5-trimethylphenoxy) -2,3-epoxypropane (II) and isopropylamine solvent at a pressure of 0.2 to 0.3 MPa and temperatures of 90 to 70 ° C.

After completion of the reaction, excess isopropylamine is distilled off under low temperature and the residue is recrystallized. An advantage of the process of the invention is the high selectivity of the reaction, the increase in the yield of 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -3-thiopropylamino-2-propanol (I), simplification of technology and the associated energy and labor savings.

Claims

In the following, the invention is illustrated by way of example, without being limited thereto. EXAMPLE 1 To a 1 L 630 L enamelled reactor equipped with a stirrer, a thermometer, a pressure gauge and a pressure relief valve, 400 L of isopropylamine was charged with a minimum of 98% and 100 kg of 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -2,3-epoxypropane. The reactor is closed, stirring is continued for 30 ml, the reactor contents are heated to 70 ° C, while the reactor pressure is increased to 0.3 MPa. The temperature was maintained under constant stirring for 1 hour. Thereafter, the reactor contents were cooled to 90 ° C and 90 to 95% isopropylamine was distilled off at atmospheric pressure. The decisopropylamine is distilled off under reduced pressure of 0.02 MPa and a maximum temperature of 50 ° C in the digester. To the concentrated portion was added 250 L of toluene-ethanol 1: 1 by volume. From this mixture, 110 kg of 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -3-iso-propylamino-2-propanol were obtained by crystallization containing min. 99%, 1- (4-hydroxy-2,3,5-trimethyl-phenoxy) -3-isopropylamino-2-propanol content below 1%. EXAMPLE 2 A procedure similar to Example 1 except that the reaction is carried out at a pressure of 0.2 MPa and a temperature of 50 ° C for 2.5 hours. PREPARATION OF THE PREPARATION 1- (4-Acetoxy-2,3,5-trimethylphenoxy) ) -3-isopropylamino-2-propanol of the formula OOCCH3 JCH3 from CH 2 CH 2 CH 2 CH 3 CH 3 CH 3 from 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -2,3-epoxypropene of the formula: Characterized in that the reaction is carried out in isopropylamine, which is the current solvent and the reaction component at a pressure of 0.2 to 0.3 MPa and a temperature of 50 to 70 ° C.