CS239414B1 - Preparation method of 1-/4-acetoxy-2,3,5-trimethylfenoxy/-3-isopropylamono-2-propanole - Google Patents

Abstract

Process for preparing 1- (4-acetoxy-2,3,5- -trimetylfenoxy) -3-isopropylamino-2-propanol of formula OCOCH3 H3 <Z CH3 ch3 ch3 O - cn 2 - CH 2 - CH 2 - NH - CH OH CH, FROM from 1- (4-acetoxy-2,3,5-trimethylphenoxy) -2,3- -epoxypropane formula o-ch 2 -CH-CH 3 IN and isopropylamine, characterized in that the reaction is carried out in isopropylamine, which is both the solvent and the reaction component are simultaneously at a pressure of 0.2 to 0.3 MPa and temperature 50-70 ° C.

Description

Process for preparing 1- (4-acetoxy-2,3,5-trimethylphenoxy) -3-isopropylamino-2-propanol of the formula

OCOCH ₃

H ₃ <Z

CH ₃ CH ₃ CH ₃

O - cn ₂ - CH - CH ₂ - NH - CH

Í ^H

OH

CH, from 1- (4-ac ethoxy-2,3,5-trimethylphenoxy) -2,3-epoxypropane of formula

o-ch ₂ CH-CH 2

V a 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.

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

OCOCH ₃

H, C (^ SCH

Uch) .CH, (I)

OH

CH, isopropylamine and from r- (4? Ap / ethoxy-2,3,5-trimethylphenoxy) -2,3-epoxypropane

CH - CH,

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

Podlá čs. No. 128471, the reaction of 1- (4-acetoxy-2,3,5-trimethylphenoxy) -2,3-epoxypropane with isopropylamine is carried out in water, aqueous C 1 -C 3 alkanol or in alkanol alone at atmospheric pressure. A disadvantage of this process is the formation of the by-product 1- (4-hydroxy-2,3,5-trimethylphenoxy) -3-isopropylamino-2-propanol of the formula

OH ^H 3 ^{C CH} 3 rho

O-CH, -CH-CH, -NH-CH

I \ _CH ,

OH .3 ^C which is produced in an amount of 3 to 5% in the course of the same reaction, saponification of the acetate group This substance is an impurity, the removal rate of a clip prípuatnú requires at least twice the crystallisation ^ ýciu. A further disadvantage of the above process is the overheating thermal stress of the reaction mixture when the solvent is distilled off, thereby reducing the quality and yield of the product.

From the process site using solvent and excess isopropylamine, it is necessary to regenerate the solvent-isopropylamine mixture by rectification, which is laborious and energy intensive.

The above disadvantages are overcome by the process according to the invention, which is characterized in that 1- (4-acetoxy-2,3,5-trimatylphenoxy) -3-isopropylamino-2-propanol (I) is prepared from 1- (4) -acetoxy-2,3,5-trimethylphenoxy) -2,3-epoxypropene (II) and isopropylamine without solvent at a pressure of 0.2 to 0.3 MPa and a temperature of 50 to 70 ° C.

After completion of the reaction, excess isopropylamine is distilled off at low temperature and the residue is recrystallized. Advantages of the process according to the invention are high selectivity of the reaction, an increase in the yield of 1- (4-acetoxy-2,3,5-trimethylphenoxy) -3-isopropylamino-2-propanol (I), simplification of the technology and the associated saving of energy and labor.

In the following, the invention is illustrated by examples without being limited thereto.

Example _x

400 L of isopropylamine of at least 98% and 100 kg of 1- (4-acetoxy-2,3,5-trimethylphenoxy) -2,3-epoxypropane are charged to 630 L of an enamelled reactor equipped with a stirrer, a thermometer, a pressure gauge and a safety valve. The reactor is sealed, agitation is started, and the reactor contents are heated to 70 ° C over 30 minutes while the reactor pressure rises to 0.3 MPa.

The temperature was maintained with stirring for 1 hour. The reactor contents were then cooled to 50 ° C and 90-95% of isopropylamine was distilled off at atmospheric pressure. The isopropylamine residue is distilled off under reduced pressure of 0.02 MPa and a maximum of 50 ° C in the digester.

To the concentrated portion is added 250 L of a 1: 1 v / v toluene-ethanol mixture.

From this mixture, 110 kg of 1- (4-acetoxy-2,3,5-trimethylphenoxy) -3-isopropylamino-2-propanol containing min. 99%, 1- (4-hydroxy-2,3,5-trimethylphenoxy) -3-isopropylamino-2-propanol content below 1%.

Example 2

The procedure of Example 1 was followed except that the reaction was carried out at a pressure of 0.2 MPa and a temperature of 50 ° C for 2.5 hours.

Claims (1)

OBJECT OF THE INVENTION Spčsob the preparation of 1- (4-acetoxy-2,3,5-trimethyl-phenoxy) -3-isopropylamino-2-propanol of formula OCOCH ₃ ^S CH ₃ / _O-CH2-CH - _CH2-NH-CH OH _CH3 CH, from 1- (4-acetoxy-2,3,5-trimethylphenoxy) -2,3-epoxypropene of formula ₃ H _{3 (} Ac) ^CH 3 M _{CH3 O-CH2-CH-CH2} o isopropylamine, characterized in that the reaction is carried out in isopropylamine that is both solvent and reactants at a pressure of 0.2 to 0.3 MPa and a temperature of 50 to 70 ° C.