CS265532B1 - 3-Acetyl-4 - [(3-bromo-2-hydroxy) propoxy] phenylcarbamic Acid Alkyl esters - Google Patents

Abstract

The solution falls into the field of organic synthesis and solves the method of preparation of new alkyl esters of 3-acetyl-4 [/3-bromo- -2-hydroxy/-propoxy| phenylcarbamic acid of general formula I, in which R is alkyl with 3 to 4 carbon atoms. The preparation is carried out by reacting the alkyl ester of 3-acetyl-4-hydroxyphenylcarbamic acid with 3-bromo-1,2-epoxypropane under basic catalysis with piperidine on a water bath or the alkyl ester of 3-acetyl- -4 Γ /2,3-epoxy/-propoxy] phenylcarbamic acid under dilution with 48% hydrobromic acid at room temperature. Compounds of this type can be used as starting materials in the preparation of biologically active substances

Description

The present invention relates to 3-acetyl-4 [(3-bromo-2-hydroxy) -propoxy] phenylcarbamic acid alkyl esters of formula X

OH

I

OCH ₂ CHCH ₂ Br I> coch ₃ (I),

NHCOOR wherein R is C 3 -C 4 alkyl, as well as a process for the preparation of these compounds.

These novel substances, which have not been described so far in the literature, of the above-mentioned meaning of R, are widely used as starting materials in the preparation of substances with biological properties (locally anesthetic, beta-adrenolytic, spasmolytic and the like).

Compounds of formula I wherein R is C 3 -C 4 alkyl can be prepared according to the invention in various ways, e.g. by reacting:

a) alkyl ester of 3-acetyl-4-hydroxyphenylcarbamic acid (U.S. Pat. No. 9,795) of the general formula II

COCH ₃

NHCOOR (II), wherein R is the same as in formula I with 3-bromo-1,2-epoxypropane under basic piperidine catalysis, according to the method described in the literature (Crowter et al. J. Med. Chem. 15 260 (1972).

b) 3-acetyl-4 '(2,3-epoxy) -propoxy] phenylcarbamic acid alkyl ester of the formula III

OCK ₂ CH-CH ₂ COCH 3

(III),

NHCOOR in which R is the same as in formula I is decomposed with 48% hydrobromic acid by the same method as described in the literature (Zóls et al. Arzneim.-Forsch. 2, 33 (1983))

Further details of the preparation of the compounds will be apparent from the following non-limiting Examples.

Example 1

23.7 g (0.1 mol) of 3-acetyl-4-hydroxyphenylcarbamic acid propyl ester, 20.6 g (0.15 mol) of 3-bromo-1,2-epoxypropane and 1 ml of piperidine are heated in a water bath for 10 h . After completion of the reaction, excess bromohydrin was distilled off in vacuo and the residue was dissolved in chloroform. The organic phase is shaken with 10% hydrochloric acid, then with water and, after drying, the chloroform is distilled off in vacuo. 3-Acetyl-4- (3-bromo-2-hydroxy) -propoxy] phenylcarbamic acid propyl ester after recrystallization from methanol or ethanol is a white crystalline solid, m.p. t. 112 DEG-115 DEG C., 76% of theory. and

Elero. anal. for C ^^^ NO ^ Br: calc. C H

N

48.14 / 48.20

5.38 / 5.37

3.74 / 3.52

Example 2

Dissolve 10.0 g (0.03 mol) of 3-acetyl-4 ', 2,3-epoxy / propoxy-phenylcarbamic acid butyl ester in 100 ml of acetone and gradually decompose at room temperature with 26 ml of acetone and gradually decompose at at room temperature with 26 ml of acetone, and gradually quenched at room temperature with a mixture of 26 ml of water and 20 ml of 48% hydrobromic acid.

After 3 h, the precipitated crystals are aspirated and washed with aqueous acetone. Butyl 3-acetyl-4 [(3-bromo-2-hydroxy) -propoxy] phenylcarbamic acid butyl ester after recrystallization from dilute ethanol is a white crystalline solid, m.p. t. 103 DEG-106 DEG C., 71% of theory.

Elero. anal. for ^l ~ -ig ^H 22 ^NO 5 ' ^{Br: off /} rent. CH

N

49.49 / 49.28

5.71 / 5.64

3.60 / 3.59

Using the methods described above, the following novel substances not described in the literature were prepared:

1, 3-acetyl-4 (3-bromo-2-hydroxy) propoxy propyl ester | phenylcarbamic T, m. 112-115 ° C (methanol) (according to Example 1 and 2)

2, 3-acetyl-4 [(3-bromo-2-hydroxy) -propoxy] butyl ester | phenylcarbamic T. t. 103 to 106 ° C (diluted ethanol) (according to Example 1 and 2)

Claims (3)

No. 3,255,532, the chloroform is distilled off under vacuum. 3-Acetyl-4- (3-bromo-2-hydroxy) propoxy] phenylcarbamic acid propyl ester, after recrystallization from methanol or ethanol, is a white crystalline solid, mp 112-115 ° C, yield 76% of theory. Elena's anal. for Ο ^^ θΝΟ ^ ΒΓ: off / load. CH N 48.14 / 48.20 5.38 / 5.37 3.74 / 3.52 Example 2 10.0 g (0.03 mol) of 3-acetyl-4H-2,3-epoxy butyl ester The propoxyphenylcarbamic acid is dissolved in 100 ml of acetone and successively decomposed at room temperature with a mixture of 26 ml of acetone and successively decomposed at room temperature with a mixture of 26 ml of acetone and gradually decomposed at room temperature with a mixture of 26 ml of water and 20 ml of 48% hydrobromic acid. After 3 h, the precipitated crystals are filtered off with suction and washed with aqueous acetone. 3-Acetyl-4 - [[3-bromo-2-hydroxy / propoxy] phenylcarbamic acid butyl ester recrystallized from dilute ethanol to give a white crystalline solid, mp 103-106 ° C, yield 71% of theory. Elena anal. for C | gH22NO5Br: off / off CH N 49.49 / 49.28 5.71 / 5.64 3.60 / 3.59 The following novel non-written references were prepared using the methods described above: 1, 3-acetyl-4β-bromo propyl ester -2-hydroxy-propoxy 112 DEG-115 DEG C. (methanol) (according to Example 1 (2)) 2, 3-acetyl-4 [(3-bromo-2-hydroxy) propoxy] butyl ester | phenylcarbamate. 103-106 ° C (diluted ethanol) (Example 1 and 2) SUBJECT OF THE INVENTION 1. Alkyl esters of 3-acetyl-4 [3-bromo-2-hydroxy] propoxy] phenylcarbamate of general formula I OH OCH2CHCH2BrCOCH3 NHCOOR wherein R is alkyl of 3 to 4 carbon atoms. 2. A process for preparing 3-acetyl-4'-3-bromo-2-hydroxy-propoxy] phenylcarbamic acid alkyl esters of the formula I as defined in claim 1, wherein the 3-acetyl-4-alkyl ester is reacted. -hydroxyphenylcarbamic acid of general formula II 265532 4 OH COCH, NHCOOR (II), wherein R is the same as in formula I with 3-bromo-1,2-epoxypropane under a basic piperidine catalysis on a water bath for 10 h. 3. A process for the preparation of alkyl esters of 3-acetyl-4- [3-bromo-2-hydroxy / propoxy] phenylcarbamic acid of the general formula I according to claim 1, characterized in that the alkyl esters of 3-acetyl-4 [72,3] are decomposed -epoxy / propoxyphenylcarbamate of the general formula (III); NHCOOR wherein R is the same as in Formula I, with 48% hydrobromic acid. (III)