Process for the preparation of pyrimidine compounds

Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...

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C07D23934

Patent

active

061629162

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BRIEF SUMMARY
The present invention relates to a process for preparing (E)-methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenoate, an intermediate in the agrochemical industry.
Methods for preparing (E)-methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenoate are described in WO 92/0870.
The present invention provides a process for preparing a compound of formula (I), comprising treating a compound of formula (II) with an acid catalyst in the presence of an acid anhydride, an acid chloride or 2-acetoxybenzonitrile at a temperature in the range 70-110.degree. C.
Acid catalysts include acids (such as sulphonic acid or a derivative thereof (for example chlorosulphonic acid, methane sulphonic acid or p-toluene sulphonic acid), hydrochloric acid or an acetic acid derivative (for example trifluoroacetic acid or di- or trichloroacetic acid)), a suitable phenol derivative (such as 2-cyanophenol) or potassium bisulfate.
Acid anhydrides are preferably C.sub.2-5 alkyl anhydrides, for example acetic anhydride.
Acid chlorides are preferably C.sub.2-5 alkyl chlorides, for example acetyl chloride or propionyl chloride.
The process of the invention can be carried out in the presence of a solvent. Such a solvent is preferably inert under the process conditions. Suitable solvents include saturated or unsaturated hydrocarbons (such as toluene, o-xylene, m-xylene, p-xylene, cyclohexane or methylcyclohexane), an ether (such as glyme or diglyme) or a ketone (such as methylisobutylketone). It is preferred that the solvent has a boiling point in the range 70-140.degree. C., especially in the range 85-120.degree. C.
In one aspect the present invention provides a process for preparing a compound of formula (I), comprising treating a compound of formula (II) with an acid catalyst in the presence of an acid anhydride.
In another aspect the present invention provides a process for preparing a compound of formula (I), comprising treating a compound of formula (II) with methane sulphonic acid, chlorosulphonic acid or 2-cyanophenol in the presence of an acid anhydride, an acid chloride or 2-acetoxybenzonitrile, the process being conducted in the presence of a solvent.
In a further aspect the present invention provides a process for preparing a compound of formula (I), comprising treating a compound of formula (II) with methane sulphonic acid or chlorosulphonic acid in the presence of an acid anhydride, the process being conducted in the presence of a solvent.
The process of the present invention can be carried out by treating a compound of formula (II) with an acid catalyst (preferably methane sulphonic acid) in the presence of an acid anhydride (especially acetic anhydride), an acid chloride (especially acetyl chloride) or 2-acetoxybenzontrile at a temperature in the range 70-110.degree. C. (especially 85-100.degree. C.) at ambient pressure.
Alternatively, the process of the present invention can be carried out by treating a compound of formula (II) with an acid catalyst (preferably methane sulphonic acid) in solvent (especially toluene or methylcyclohexane) in presence of a suitable acid anhydride (especially acetic anhydride) at a temperature in range 70-110.degree. C. (especially 85-100.degree. C.) at ambient pressure.
In a further aspect the present invention provides a process for preparing a compound of formula (I) comprising treating a compound of formula (II) (1 equivalent) with methane sulphonic acid (about 0.05 equivalents) in the presence of acetic anhydride (about 1 equivalent, preferably 1 to 1.1 equivalents) at a temperature in the range 85-105.degree. C. (especially 90-95.degree. C.), the process being carried out in the absence of a solvent.
It is preferred that, when the process is carried out in the absence of a solvent, the compound of formula (I) is isolated by: (i) distilling off by-products (preferably at a temperature in the range 50-150.degree. C. and under atmospheric pressure), (ii) partitioning the resulting residue between an organic solvent (such as toluene or a xylene) and water, and (iii) evaporati

REFERENCES:
patent: 5773445 (1998-06-01), Gayer
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G. Gross et al., Chemical Synthesis of .alpha.-Formylphenylacetic Acid, the Postulated Precursor of Tropic Acid, 36 Z. Naturforsch, 611-614 (1981).
R. Eade et al. C-Glycosylflavonoids. The Synthesis of 7,4'Di-0-methylpuerarin (*-C-.beta.-D-Glucopyranosyl-74,'-dimethoxyisoflavone), Aust. J. Chem, 2699-2706 (1978).

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