Method for preparing a pyripyropene compound

Patent metadata

Field	Value
Publication number	US-9598428-B2
Application number	US-201414760302-A
Country	US
Kind code	B2
Filing date	Jan 15, 2014
Priority date	Jan 16, 2013
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

The present invention relates to a method for preparing the pyripyropene compound of the formula (I) which method comprises the following steps: i) subjecting a pyripyropene compound of formula Pyripyropene A to an alkaline hydrolysis to yield a 1,7,11 -trideacetylpyripyropene A, ii) reacting 1,7,11-trideacetylpyripyropene A obtained in step i) with cyclopropane carbonyl chloride to yield a raw product containing the pyripyropene compound of formula (I); iii) subjecting the raw product of step ii) to crystallization to yield a crystalline pyripyropene compound of formula (I) and a mother liquor; and iv) recycling the mother liquor or a pyripyropene compound containing fraction thereof to the alkaline hydrolysis of step i).

First claim

We claim:

1. A method for preparing the pyripyropene compound of the formula I

the method comprising the following steps:
i) subjecting a pyripyropene compound of formula II to an alkaline hydrolysis to yield a pyripyropene compound of the formula III,

ii) reacting the pyripyropene compound of formula III obtained in step i) with cyclopropane carbonyl chloride to yield a raw product containing the pyripyropene compound of formula I;
iii) subjecting the raw product of step ii) to crystallization to yield a crystalline pyripyropene compound of formula I and a mother liquor; and
iv) recycling the mother liquor or a pyripyropene compound containing fraction thereof to the alkaline hydrolysis of step i) by one of the following measures:
combining the mother liquor or pyripyropene compound containing fraction thereof with fresh compound of the formula II and subjecting the thus obtained mixture to the alkaline hydrolysis of step i);
subjecting the pyripyropene compounds contained in the mother liquor to an alkaline hydrolysis to achieve an at least partial hydrolysis of the ester groups present in the pyripyropene compounds contained in the mother liquor, adding to the thus obtained mixture fresh compound of formula II and continuing the alkaline hydrolysis; or
subjecting fresh compound of formula II to an alkaline hydrolysis to achieve an at least partial hydrolysis of the ester groups present therein, adding to the thus obtained mixture the pyripyropene compounds contained in the mother liquor and continuing the alkaline hydrolysis.

2. The method of claim 1 , wherein step ii) is performed in a solution or suspension of the compound of formula III in a polar aprotic solvent, which is selected from N-methyl pyrrolidone and dimethyl acetamide.

3. The method of claim 2 , wherein the weight ratio of polar aprotic solvent to compound III is from 6:1 to 1:1.

4. The method of claim 1 , wherein the reaction mixture of step ii) is subjected to an aqueous extraction with an acidic aqueous extractant.

5. The method of claim 1 , wherein the reaction mixture of step ii) is subjected to a workup comprising a neutralization of the reaction mixture and a subsequent aqueous extraction with an acidic aqueous extractant.

6. The method of claim 4 , wherein the acidic aqueous extractant contains phosphoric acid.

7. The method of claim 1 , wherein the crystallization of the raw product is achieved from a solution of the raw product in at least one organic solvent, which solvent comprises at least 50%, based on the total amount of solvent, of at least one aprotic solvent selected from aromatic hydrocarbon solvent, C 1 -C 4 -alkyl acetates and mixtures thereof.

8. The method of claim 1 , wherein the relative amount of the pyripyropene compound of formula II and mother liquor or pyripyropene compound containing fraction recycled into the alkaline hydrolysis of step i) is such that molar ratio of the recycled pyripyropene compound and fresh pyripyropene of formula II is in the range from 1:5 to 5:1.

9. The method of claim 1 , wherein hydrolysis in step i) is achieved by reacting the compound of formula II with a base selected from the group consisting of alkali metal hydroxide, earth alkaline metal hydroxides, alkali metal C 1 -C 4 -alkoxides and earth alkaline metal C 1 -C 4 -alkoxides, in an organic solvent or in a mixture of an organic solvent with water.

10. The method of claim 9 , wherein the organic solvent comprises at least one C 1 -C 4 -alkanol.

11. The method of claim 9 , wherein the organic solvent comprises at least 90%, based on the total amount of organic solvent, of a mixture of at least one alkyl aromatic hydrocarbon solvent, and at least one C 1 -C 4 -alkanol.

12. The method of claim 8 , wherein the relative amount of the pyripyropene compound of formula II and mother liquor or pyripyropene compound containing fraction recycled into the alkaline hydrolysis of step i) is such that molar ratio of the recycled pyripyropene compound and fresh pyripyropene of formula II is in the range from 1:3 to 3:1.

13. The method of claim 9 , wherein the base is selected from the group consisting of sodium hydroxide and sodium methoxide.

14. The method of claim 10 , wherein the organic solvent comprises methanol.

15. The method of claim 11 , wherein the organic solvent comprises at least 90%, based on the total amount of organic solvent, of a mixture of toluene and/or ethyl benzene, and methanol.

Assignees

• Basf Se

Inventors

• Bonnekessel Melanie
• Reichert Wolfgang
• Hoock Ralf
• Kaeding Thomas
• Koradin Christopher
• Pletsch Andreas
• Ehresmann Manfred
• Schroeder Hartwig

Classifications

• A01N53/00

  Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof · CPC title

• A01N43/90

  having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system · CPC title

• C07D493/04 Primary

  Ortho-condensed systems · CPC title