Patent Watch

December 17, 2012

Two steps are better than one in the synthesis of an agrochemical intermediate. N. Lui and S. Antons disclose a method for preparing compounds that are intermediates for manufacturing agrochemical ingredients. The examples in the patent specifically cover the preparation of difluoromethyl compound 4 by a two-step process shown in the figure.

The first step is heating amine 1 and fluoroester 2 with no solvent at reflux to produce amide 3. After the EtOH byproduct is distilled off, 3 is recovered in 99% yield and 99% purity. It is then reduced with RhCl3–PhSiH3 in a hydrogen-transfer reaction to give amine 4 in 95% yield and 98% purity.

The amide can also be reduced with NaBH4–BF3·Et2O to obtain 4 in 90% yield and 95% purity. The inventors’ claims focus on the reduction of the amide to the amine and cover several other alternative methods for this reaction.

An existing one-step method involves the alkylation of 5 with 6. This reaction, however, leads to polyalkylation of the nitrogen atom, and the yield of 4 is only 53%. Advantages of the two-step processes are that they give high product yields without the need to purify the intermediate amide. (Bayer Cropscience AG [Monhein, Germany]. US Patent 8,273,897, Sept. 25, 2012; Keith Turner)

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