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filingDate 1989-05-30-04:00^^<http://www.w3.org/2001/XMLSchema#date>
grantDate 1990-02-13-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_9445d1df74b841ddcbfb9c576845b309
publicationDate 1990-02-13-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber US-4900860-A
titleOfInvention Process for preparing phosphonyloxyacyl amino acids
abstract A process is provided for preparing phosphonyloxyacylamino acids and derivatives thereof having the structure <IMAGE> wherein X is <IMAGE> <IMAGE> +TR <IMAGE> which includes the steps of treating a phosphonic acid dichloride of the structure <IMAGE> with an alpha -hydroxy acid of the structure <IMAGE> in the presence of base such as triethylamine at reduced temperatures to form the cyclic mixed anhydride of the structure <IMAGE> (which is a new intermediate) and reacting the cyclic mixed anhydride with an amino acid or ester of the structure HX in the presence of base such as triethylamine produces the ACE inhibitor compound <IMAGE> In an alternative process, the cyclic anhydride is quenched with water to form the diacid <IMAGE> which is treated with a condensing agent such as dicyclohexyl carbodiimide (DCC), 1,1-carbonyldiimidazole (CDI) or thionyl chloride followed by quenching with the amino acid HX produces the above ACE inhibitor compound. In another variation of the process of the invention, the above cyclic anhydride is treated with an alcohol of the structure R3OH to form the phosphonic acid diester <IMAGE> which may be coupled with the amino acid or ester HX to form the ACE inhibitor <IMAGE>
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