KR970065528A - Reactive phosphate derivative of novel thia (diazo) acetic acid and process for its production - Google Patents

Abstract

The present invention relates to a novel reactive thia (diazo) acetic acid phosphate derivative (hereinafter referred to as a "reactive organic acid derivative") represented by the following general formula (I) which can be used very effectively in the production of a? -Lactam antibiotic, And a method for producing the same.

Wherein R ¹ represents hydrogen or an amino protecting group and R ² represents hydrogen, C ₁ -C ₄ alkyl or -C (R ^a ) (R ^b ) CO ₂ R ^c , wherein R ^a and ^b are each Independently of _{one another} , represent C ₁ -C ₄ alkyl or together with the carbon atom to which they are attached may form a C ₃ -C ₇ cycloalkyl, R ^c represents hydrogen or a carboxy protecting group and R ³ represents C ₁ -C ₄ alkyl or phenyl, or together with the oxygen and phosphorus to which R ³ is attached may form a 5- to 6-membered heterocycle, R ⁴ and R ⁵ are each independently hydrogen, C ₁ -C ₄ alkyl or Phenyl, and Q represents N or CH.

Description

Reactive phosphate derivative of novel thia (diazo) acetic acid and process for its production

Since this is a trivial issue, I did not include the contents of the text.

Claims (13)

Reactive phosphate derivatives of thia (diazo) acetic acid of general formula (I) Wherein R ¹ represents hydrogen or an amino protecting group and R ² represents hydrogen, C ₁ -C ₄ alkyl or -C (R ^a ) (R ^b ) CO ₂ R ^c , wherein R ^a and ^b are each Independently of _{one another} , represent C ₁ -C ₄ alkyl or together with the carbon atom to which they are attached may form a C ₃ -C ₇ cycloalkyl, R ^c represents hydrogen or a carboxy protecting group and R ³ represents C ₁ -C ₄ alkyl or phenyl, or together with the oxygen and phosphorus to which R ³ is attached may form a 5- to 6-membered heterocycle, R ⁴ and R ⁵ are each independently hydrogen, C ₁ -C ₄ alkyl or Phenyl, and Q represents N or CH. The method of claim 1, wherein, R ¹ is hydrogen or triphenyl methyl; R ² is hydrogen, C ¹ -C ² alkyl or t-butoxycarbonyl isopropyl; R ³ is methyl, ethyl, isopropyl or phenyl; R ⁴ and R ⁵ are each independently hydrogen, C ₁ -C ₂ alkyl or phenyl; Q is N or CH. 3. The compound according to claim 2, which is methyl N-phenylphosphoramido (Z) - (2-aminothiazol-4-yl) methoxyiminoacetate; Ethyl N-phenylphosphoramido (Z) - (2-aminothiazol-4-yl) methoxyiminoacetate; (Z) - (2-aminothiazol-4-yl) methoxyiminoacetate or methyl N-phenylphosphoramido (Z) 4-yl) -2- (t-butoxycarbonyl) isopropoxyiminoacetate. A process for producing a reactive organic acid derivative represented by the following general formula (I) by reacting an organic acid of the following general formula (II) with a chlorophosphate derivative of the general formula (III) in a solvent and in the presence of a catalyst. Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and Q are as defined in claim 1. The method according to claim 4, wherein the compound of formula (III) is used in an amount of 0.5 to 2.0 equivalents based on the organic acid of formula (II). The method of claim 4, wherein the solvent is selected from the group consisting of dichloromethane, dimethylacetone, N, N-dimethylformamide and N, N-dimethylacetamide, dichloroethane, chloroform, carbon tetrachloride, toluene, xylene, acetonitrile, ethyl acetate, dioxane, N-dimethylacetamide. ≪ / RTI > 5. The method of claim 4 wherein the base is selected from the group consisting of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, triethylamine, triethylenediamine, tri (n-butyl) amine, diisopropylethylamine, Lt; / RTI > aniline. 85. The process of claim 84, wherein the catalyst is at least one selected from the group consisting of tertiary amines, quaternary ammonium and phosphonium compounds. The process according to claim 8, wherein the catalyst is 1,4-diazabicyclo [2,2,2] octane, tetra-n-butylammonium bromide or tetra-n-butylphosphonium bromide. The process according to claim 8, wherein the catalyst is used in a molar ratio of from 0.1 to 50% with respect to the organic acid of formula (II). The process according to claim 10, wherein the catalyst is used in a molar ratio of 0.5 to 5% with respect to the organic acid of formula (II). 5. The process of claim 4 wherein the reaction is carried out in a temperature range of from -40 to 60 < 0 > C. 13. The method of claim 12, wherein the reaction is carried out at a temperature ranging from 0 to 20 < 0 > C. ※ Note: It is disclosed by the contents of the first application.