Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1999-06-10
2000-11-28
Ford, John M.
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C07D23952
Patent
active
061537500
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a process for the preparation of (E)-methyl 2-[2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxyprop enoate, a plant fungicide.
Methods of preparing (E)-methyl 2-[2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxypropenoate, and intermediates therefor, are described in EP-A2-0382375, WO 92/08703, GB2291874 and PCT Application No. PCT/GB97/02015. The method for preparing (E)-methyl 2-[2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxypropenoate described in WO 92/08703 involves heating a mixture of (E)-methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenoate, 2-cyanophenol, potassium carbonate and cuprous chloride in N,N-dimethylformamide at 120.degree. C. for 90 minutes. The method described in PCT/GB97/02015 involves heating methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropanoate with 2-cyanophenol at 90-95.degree. C. to form (E)-methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenoate which is then heated to 120-125.degree. C. in N,N-dimethylformamide with potassium carbonate to form the desired product.
The present invention provides a process for preparing (E)-methyl 2-[2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxypropenoate comprising contacting (E)-methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenoate or methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropanoate with 2-cyanophenate anions, the process being conducted in the absence of copper or a copper salt and in the absence of N,N-dimethylformamide.
The process of the invention may be conducted in the complete absence of any solvent or mixture of solvents, miscible or immiscible, including water itself. In this case the reaction mixture will be in the form of a melt.
Alternatively, the process may be conducted using water as the only solvent. In this case the water may be generated in situ or may be specifically added, or both. Water is generated in situ when an appropriate base is used to generate 2-cyanophenate anions in situ with 2-cyanophenol, as will be the usual procedure. Such a base will be, for example, a hydroxide, carbonate or bicarbonate. Bases which can be used which do not generate water in situ include phosphates and tertiary amines.
The process may also be conducted in the presence of a water-immiscible solvent or a mixture of water-immiscible solvents in the complete absence of water, with water generated only in situ or with added water and/or water generated in situ. Where water is present with a water-immiscible solvent or mixture of water-immiscible solvents, the process will take place in a two phase liquid system. Preferred water-immiscible solvents include cyclic hydrocarbons, such as aromatic hydrocarbons, for example toluene and xylenes, and alicyclic hydrocarbons, for example methylcyclohexane.
The process may also be conducted in the presence of other solvents which may be miscible, immiscible or partially miscible with water, including alcohols such as 2-propanol, 1-butanol, 2-pentanol and cyclohexanol, ketones such as methyl ethyl ketone, methyl iso-butyl ketone and 2,4-dimethyl-3-pentanone, ethers such as tert-butyl methyl ether, glymes such as 2-methoxyethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether and esters such as ethyl acetate and iso-butyl acetate.
Thus the process of the invention includes the use of any suitable solvent other than N,N-dimethylformamide.
2-Cyanophenate anions can be used directly in the process of the present invention, for example by using an alkali metal 2-cyanophenate (such as sodium or potassium 2-cyanophenate). Alternatively, 2-cyanophenate anions can be prepared in situ by reacting 2-cyanophenol with a suitable base, which may be a suitable hydroxide such as an alkali metal hydroxide, for example sodium or potassium hydroxide, a suitable carbonate such as an alkali metal carbonate, for example sodium or potassium carbonate, a suitable bicarbonate such as an alkali metal bicarbonate, for example sodium or potassium bicarbonate, a suitable p
Ewins Robert Comgall
Fleming Ian George
Jones Raymond Vincent Heavon
McNeish Samuel
Whitton Alan John
Ford John M.
Savitsky Thomas R.
Zeneca Limited
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