KR950006149B1 - Novel n-(2-haloalkanoyloxy)succinimide derivative and manufacturing method thereof - Google Patents

Abstract

The novel N-(2-haloalkanoyloxy)succinimide derivatives of formula (I) where R1, R2 = H or lower alkyl, X = chloride or bromide.

Description

Novel N- (2-haloalkanoyloxy) succinimide derivatives and preparation method thereof

The present invention is a novel N- (2-haloalkanoyloxy) of formula (I), which is used as an important intermediate in the preparation of enalapril, which is used as an angiotensin converting enzyme inhibitor and an antihypertensive agent A succinimide derivative and a method for producing the same.

Wherein R ¹ , R ² is hydrogen, an aryl group such as a lower alkyl group of C ₁ -C ₁₀ , a cyclic alkyl group, an alkenyl group or a wasteyl, and X is chlorine, bromine or iodine.

The compound of the general formula (I) is obtained by reacting N-hydroxysuccinimide of the following general formula (II) with an acyl halide of the structure of the following general formula (III).

Wherein R ¹ , R ² and X are the same as in general formula (I), and Y is chlorine or bromine.

The present invention is briefly described as follows. N-hydroxysuccinimide of formula (II) is dissolved in N, N'-dimethylformamide or other conventional solvents in the presence of tertiary amines such as triethylamine, trimethylamine, pyridine, and the like. Dilute acyl halide of formula (III) is slowly added at room temperature. The reaction proceeds very quickly and should be stirred sufficiently. After the reaction, the solvent is removed by distillation under reduced pressure in a rotary distillation unit to obtain a target substance. The novel N- (2-haloalkanoyloxy) succinimide derivatives of formula (I) thus obtained can be used as major intermediates in the preparation of angiotensiphone enzyme inhibitors such as enalapril and other antihypertensive agents. It is a novel compound.

The following examples describe specific examples of the preparation of novel compounds of the present invention.

Example 1

Preparation of N- (2-bromopropionyloxy) succinimide.

After dissolving 5.75 g of N-hydroxysuccinimide and 5.05 g of triethylamine in 50 ml of N, N'-dimethylformamide, 10.8 g of 2-bromopropionyl bromide was added to 20 ml of N, N The solution dissolved in '-dimethylformamide was slowly added dropwise at room temperature drop by drop. After completion of the dropwise addition, the mixture was stirred at room temperature for one hour, 250 ml of ethyl acetate was added to the reaction mixture, washed with water three to four times, and the solvent was removed by distillation under reduced pressure in a rotary distillation unit. The product was purified by ethyl ether to give 10.50 g (yield: 84%) of high purity N- (2-bromopropionyloxy) succinimide.

¹ H-NMR (CDCl ₃ , TMS internal standard, ppm); 1.9-2.0 (d, 3H), 2.9 (s, 4H), 4.5-4.8 (q, 1H)

Example 2

Preparation of N- (2-bromopropionyloxy) succinimide.

After dissolving 5.75 g of N-hydroxysuccinimide and 5.05 g of triethylamine in 50 ml of N, N'-dimethylformamide, 8.57 g of 2-bromopropionyl bromide was added to 20 ml of N, N The solution dissolved in '-dimethylformamide was slowly added dropwise at room temperature drop by drop. After completion of the dropwise addition, the mixture was stirred at room temperature for one hour, 250 ml of ethyl acetate was added to the reaction mixture, washed with water three to four times, and the solvent was removed by distillation under reduced pressure in a rotary distillation unit. The product was purified by ethyl ether to obtain 9.75 g of high purity N- (2-bromopropionyloxy) succinimide. It was confirmed that the obtained target compound was the same compound as the compound obtained in Example 1.

Example 3

Preparation of N- (2-chloropropionyloxy) succinimide.

5.75 g of N-hydroxysuccinimide and 5.05 g of triethylamine were dissolved in 50 ml of N, N'-dimethylformamide, followed by 6.35 g of 2-chloropropionyl chloride in 20 ml of N, N. The solution dissolved in '-dimethylformamide was slowly added dropwise at room temperature drop by drop. After completion of the dropwise addition, the mixture was stirred at room temperature for one hour, 250 ml of ethyl acetate was added to the reaction mixture, washed with water three to four times, and the solvent was removed by distillation under reduced pressure in a rotary distillation unit. The product was purified by ethyl ether to obtain 8.01 g of high purity N- (2-chloropropionyloxy) succinimide.

¹ H-NMR (CDCl ₃ , TMS internal standard, ppm); 1.9-2.0 (d, 3H), 2.9 (s, 4H), 4.5-4.8 (q, 1H)

Example 4

Preparation of N- (2-chloropropionyloxy) succinimide.

5.75 g of N-hydroxysuccinimide and a calculated amount of pyridine are dissolved in 50 ml of N, N'-dimethylformamide, followed by 8.57 g of 2-chloropropionylchloride in 20 ml of N, N'-dimethyl. The solution dissolved in formamide was slowly added dropwise at room temperature drop by drop. After completion of the dropping, the mixture was stirred at room temperature for one hour, 250 ml of ethyl acetate was added to the reaction mixture, washed with water three to four times, and the solvent was removed by distillation under reduced pressure in a rotary distillation unit. The product was purified by ethyl ether to obtain 8.43 g of high purity N- (2-chloropropionyloxy) succinimide.

Claims (3)

New N- (2-haloalkanoyloxy) succinimide derivative of the following general formula (I). Wherein R ¹ and R ² are each hydrogen or a lower alkyl group, and X is chlorine or bromine. N- (2) of general formula (I) characterized by reacting N-hydroxysuccinimide of formula (II) and acyl halide of formula (III) in an organic solvent in the presence of a tertiary organic amine Method for producing haloalkanoyloxy) succinimide. Wherein R ¹ and R ² are each hydrogen or a lower alkyl group, and X and Y are each chlorine or bromine. The process of claim 2, wherein an organic amine selected from trimethylamine, triethylamine and pyridine is used as tertiary organic amine.