Organic compounds -- part of the class 532-570 series – Organic compounds – Imidate esters
Reexamination Certificate
2002-10-02
2004-10-19
Davis, Brian (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Imidate esters
Reexamination Certificate
active
06806380
ABSTRACT:
This application claims benefit of Provisional 60/326,662 filed Oct. 2, 2001.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a safe, efficient and scalable process for preparing imidoesters without the use of hydrogen chloride gas.
2. Description of the Related Art
Imidoesters, also known as imino esters, imidates and imino ethers, are useful building blocks for the synthesis of heterocyclic ring systems, such as oxazoles, imidazoles and their benzo-derivatives. They are also useful intermediates in the conversion of nitrites to esters and for the preparation of amidines, which are important heterocyclic building blocks. March, J. in “Advanced Organic Chemistry,” 3
rd
edition, pp 792-793, John Wiley and Sons, New York, 1985.
Imidoesters are typically synthesized via the Pinner reaction, wherein a nitrile and an alcohol in an anhydrous solvent are treated with a large excess of anhydrous hydrogen chloride gas. See, for example, Roger, R.;
Chem. Rev
. 1961, 61, 179
, Organic Synthesis Coll. Vol
. 2, 284 (1943), and Dox,
Org. Synth. Coll. Vol
. 1, 5 (1941). However, a base catalyzed method for producing imidoesters has been disclosed. Schaefer, F. C.; Peters, G. A.
J.Org. Chem
., 1961, 26, 412.
A significant defect with this method is the use of a large excess of the highly toxic, corrosive, and hard to handle hydrogen chloride gas. In the laboratory setting, it can be very difficult to determine exactly how much gas has been added to the reaction mixture, and consequently, a large excess of this very corrosive reagent is invariably used.
A method is desired for the preparation of imidoesters that uses the safer hydrogen chloride solutions, which are easy to handle, made by highly trained individuals using very safe, industrial procedures, and contain a well defined amount of hydrogen chloride per unit volume of solvent. Pre-made hydrogen chloride solutions are also economical because large excesses of the solutions are not required.
SUMMARY OF THE INVENTION
This invention provides for a safe and economical process for preparing imidoesters from nitrites. Specifically, the method of the present invention calls for the treatment of an anhydrous mixture of nitrile, alcohol, and solvent with anhydrous hydrogen chloride solution to form an imidoester. These compounds are useful building blocks for the synthesis of heterocyclic ring systems, such as oxazoles, imidazoles and their benzo-derivatives. They are also useful intermediates in the conversion of nitrites to esters. Specifically, the method comprises:
A) treating a nitrile with an anhydrous hydrogen chloride solution and an anhydrous alcohol, and
B) isolating the imidoester salt.
REFERENCES:
Database CAPLUS on STN, Acc. No. 1992:128187, EP 463676, Jan. 2, 1992 (abstract).*
Database CAPLUS on STN, Acc. No. 1979:611002, Pantev et al., Farmatsiya (Sofia, Bulgaria) (1979), 29(2), p. 1-5 (abstract).*
e-ROS, electronic Encyclopedia for Organic Synthesis, 2001-2003, John Wiley & Sons, Hydrogen Chloride, p. 1-15, http://www.mrw.interscience.wiley.com/eros.
Kanamarlapudi Ramanaiah C.
Khan Gaznabi
Kolb Hartmuth C.
Richardson Paul F.
Davis Brian
Lexicon Pharmaceuticals, Inc.
McDonnell Boehnen & Hulbert & Berghoff LLP
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