JPS6114147B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel 3-substituted-3-alkoxycarbonyl-2-piperidones. More specifically, the present invention is based on the following general formula () (In the above general formula (), R ₁ represents an aralkyl group or an aryl group having 20 or less carbon atoms, and R ₂ represents an alkyl group having 20 or less carbon atoms.) 3-Substituted-3-alkoxycarbonyl- Regarding 2-piperidone. When the compound of the present invention, 3-substituted-3-alkoxycarbonyl-2-piperidone, is hydrolyzed and then guanidized and esterified, the 2-substituted-
5-guanidinovaleric acid ester is obtained. 2-
Since 5-guanidinovalerate esters have an enzyme inhibitory effect (Japanese Patent Publication No. 47-21977), substituted-5-guanidinovaleric acid esters are expected to have a similar enzyme inhibitory effect. To explain the present invention in detail, the compound of the present invention, 3-substituted-3-alkoxycarbonyl-2-piperidone, is represented by the above general formula (), and in the above general formula (), R ₁ usually has 20 carbon atoms. Represents the following aralkyl group or aryl group, specifically
R ₁ is an aralkyl group such as a benzyl group, phenethyl group, 1-naphthylmethyl group, or 2-(1-naphthyl)ethyl group, or an aryl group such as a phenyl group, tolyl group, or naphthyl group. In addition, R ₂ is a methyl group, an ethyl group, a propyl group,
It usually represents an alkyl group having 20 or less carbon atoms such as isopropyl group, butyl group, t-butyl group. It is a compound of the present invention. 3-Substituted-3-alkoxycarbonyl-2-piperidone can be manufactured by various methods, and as one example, a manufacturing method represented by the following reaction formula will be explained below. That is, 3-substituted-3-alkoxycarbonyl-2-piperidone is obtained by catalytic reduction of α-substituted-α-(2-cyanoethyl)malonic acid ester represented by the above general formula () in the presence of a hydrogen-activated catalyst. It will be done. α-Substituted-α used as raw material in the above reaction
-(2-cyanoethyl)malonic acid ester is represented by the above general formula (), and in the above general formula (), R ₁ and R ₂ are as defined in the above general formula (). α-Substituted-α-(2-cyanoethyl)malonic acid esters are base-catalyzed (KOH, NaOH, K ₂ CO ₃ ,
It is produced by reacting an α-substituted malonic acid ester with acrylonitrile in the presence of a compound such as Triton B, sodium alcoholate, etc.). The ring base catalysts used in the catalytic reduction are catalysts commonly used for reduction, such as nickel-based catalysts such as Raney nickel and diatomaceous earth; Raney cobalt; noble metal-based catalysts such as palladium, platinum, rhodium, and ruthenium. The amount of catalyst used is 1/1000 to 1/5 of α-substituted-α-(2-cyanoethyl) malonic acid ester.
(weight). The reduction reaction takes place in a solvent, but as a solvent,
Examples include alcohols such as methanol and ethanol; ethers such as dioxane and tetrahydrofuran; the amount of solvent used is α-substituted-α-(2-
2 to 50 for cyanoethyl) malonic acid ester
It is twice (weight). The hydrogen pressure is usually from normal pressure to 200 Kg/cm ² , preferably from 5 to 150 Kg/cm ² . The reaction temperature is usually room temperature to 200°C, preferably 50° to 150°C. The reaction time varies depending on the reaction temperature, hydrogen pressure, type of catalyst, and amount used, but is usually in the range of 10 minutes to 15 hours. Usually, the reaction is stopped when 2 moles of hydrogen are absorbed per 1 mole of α-substituted-α-(2-cyanoethyl)malonic acid ester. After the reaction is complete, the catalyst is removed, the solvent is distilled off, and the residue is recrystallized using a suitable solvent such as a hydrocarbon solvent to obtain highly pure 3-substituted-3-alkoxycarbonyl-2-piperidone in good yield. be obtained. Next, the manufacturing method of the compound of the present invention will be specifically explained in Examples, but the compounds included in the present invention are limited to the compounds synthesized in the following Examples unless it goes beyond the gist of the present invention. It's not a thing. Example 1 α-phenyl-α- in 1.00 ml autoclave
(2-cyanoethyl)ethyl malonate 8.67g
(0.03 mol) dissolved in 23 ml of ethanol and
Add 0.4g of Ni-SiO _{2 ,} hydrogen pressure 80Kg/cm ² , temperature 100℃
When shaken for 5 hours, 0.06 mole of hydrogen is absorbed. The catalyst is removed, the solvent is distilled off, and the residue is recrystallized from benzene to obtain crystals of 3-phenyl-3-ethoxycarbonyl-2-piperidone. Melting point 143-145℃, yield 5.1g (yield 69%) Elemental analysis value: C ₁₄ H ₁₇ NO ₃ Calculated value (%) 67.99 6.93 5.66 Experimental value (%) 67.82 6.91 5.51 Example 2 ~ 4 The compounds shown in the table below were prepared according to Example 1 under the reaction conditions shown in the table. 【table】

Claims (1)

[Claims] 1. The following general formula () (In the above general formula (), R ₁ represents an aralkyl group or an aryl group having 20 or less carbon atoms, and R ₂ represents an alkyl group having 20 or less carbon atoms.) 3-Substituted-3-alkoxycarbonyl- 2-Piperidone.