SU1077881A1 - Process for preparing n-cyclohexyloxycarbonyl derivatives of amino acids - Google Patents

Abstract

A method for producing N-cyclohexyloxy-ronyl derivatives of amino acids by acylation of amino acids in an aqueous-organic medium cyclohextoxycarbonylating agent in the presence of a base, so that it can be used in order to simplify the process, as an example, in order to simplify the process, it becomes cyclohexextroxy-benched;

Description

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This invention relates to a process for the preparation of L-cyclo-xyloxycarbonyl derivatives of amino acids, which are used as intermediates in the synthesis of peptides.

The known method is obtained by 1 N-cyclohexyloxycarbonyl amino acid derivatives, based on the acylation of the amino acids cyclohexyloxycarbonyl chloride in an aqueous-organic medium in the presence of Cl3 base.

The disadvantage of this method is the use of cyclohexyloxycarboyl chloride as the acylating agent, which is unstable during long-term storage and has the properties of a lacrimator. In addition, the synthesis of cyclohexyloxycarbonyl chloride is based on the use of phosgene, which is) CO. Dicyclohexypexycarbonate does not have lacrimator properties and is stable during long-term storage. Example 1, dicyclohexylpyrocarbonate, In a suspension of sodium cyclohexylate, obtained by dissolving 23 g of metallic sodium in 100 ml of cyclohexyl alcohol, dry carbon dioxide was introduced into 800 ml of toluene and. the reaction mixture is cooled to 10 ° C. 100 ml of dimethylformamide is added and, with stirring, 70 g of benzene sulfonyl chloride are added dropwise. The reaction mixture is then stirred for 1.5-2 hours at lO-lS C and left for 12 hours at 20 ° C. Then the reaction mixture was stirred half an hour for 2 hours at 20 ° C, water was added, the aqueous layer was separated, the organic layer was washed with water, dried over anhydrous sodium sulfate and evaporated in vacuo. The residue is taken up in 100 ml of petroleum ether, filtered through a layer of silica gel, the silica gel is washed with 100 ml of petroleum ether, the combined filtrate is evaporated in vacuo. The residue is distilled under vacuum. As a result, 45 (43%) dicyclohexylpyrocarbonate are obtained, b.p. 124-126s / O, mm Hg, so pl. 2E-31 ° C. Found,%: C 61.80; H 7.90, Ci4 "2205 Calculated,%: C 62.20; H 8.20. IR spectrum: 1820, 1760, 1180, 1160 cm-1, Example 2, Cyclohexyloxycarbonylglycine, To a solution of 0.75 g, (10 mmol) glycine in 10 ml of 1 M solution., Add 3, 2 g (12 mmol) dicyclohec of oylpyrocarbonate in 5 ml of isopropyl alcohol. The reaction mixture

ry is a highly toxic compound.

The aim of the invention is to simplify the process for the preparation of N-cyclohexyl arbonyl amino acid derivatives.

The goal is achieved by the fact that according to the method for producing N-cyclohexyloxycarbonyl derivatives of amino kiosks, which consists in the fact that the corresponding amino acid is acylated in a water-organic medium, the cyclohexyloxycarbonylating agent in the presence of a base, as cyclohexyloxycarbonylating agent, use dicyclohexylpyrocarbonate,

Dicyclohexylpyrocarbonate is obtained from sodium cyclohexylate according to the following scheme: il oc-0-C-o-Ce CeHsSOgCl W II 11 00 is stirred for 1 hour at 35-40 ° C, diluted with water to 50 ml, extracted with a mixture of 5 ml of ether and 10 ml of petroleum ether The extract was washed with a 5: 1 M K 2 CO 3 solution, the aqueous layer was separated, acidified with 2N H solution, SO. to pH 2 and extracted with 40 ml of ethyl acetate. The extract is washed with water, saturated solution of 4 NaC, and dried over anhydrous sodium sulphate and evaporated in vacuo at. The residue is dissolved in ether, petroleum ether is added and the mixture is stirred in the refrigerator. The precipitated crystalline precipitate is filtered off, washed with hexane and dried in vacuum. In the end, 1.7 g (84%) of the desired product with t, pl. 99-100 ° C. Literary data, PL, 9799 ° C, Primerz. N-Cyclohexyloxycarbonyl-b-alanine. Prepared analogously to Example 2 with the difference that. L-alanine is used as the starting compound and the target product is isolated in the form of a salt with dicyclohexylamine. The result is a yield of 81% of a spruce product in the form of a salt with dicyclohexylamine, t, mp, 15 € -15 V s, 6 ° ( DMF), Found,%: with 66.9 N, 9.7; N 6.9. Calculated,%: From € 6,6; H 10.0; N 7.0. Example 4, N-Cyclohexypoxycarbonyl-b-valine. Analogously to Example 2 with the difference that L-Valine was used as the starting compound and the final product was isolated as a salt with dicyclohexylamine. Yield 70%; m.p. 148-149 with, (DMF),

Claims (1)

METHOD FOR PRODUCING N-CYCLOHEXYloxyxycarbonyl derivatives of amino acids by acylating amino acids in an aqueous organic medium with a cyclohex by a hydroxycarbonylating agent in the presence of a base, characterized in that, in order to simplify the process, dicyclohexate is used as a cyclohexyloxycarbonylating agent. > 1077881