E.i. Dupont De Nemours and Company

Fmc Corporation

Axonyx, Inc.

Joerg Bruening

Rafael Shapiro

Vladimir Grushin

Gary David Annis

Donald J Dumas

Albert Loren Casalnuovo

Junbae Hong

A method for preparing a compound of Formula (1) and compounds therefrom, comprising treating a compound of Formula (2) to provide a compound of Formula (5) and treating the compound of Formula (5) with a hydroxylamine salt wherein R, Rand m are as defined in the specification. The compound of Formula (1), prepared by the above method, can be used to prepare a compound of Formula (8) wherein R, R, Rand m are as defined in the specification.

Process for synthesis of a 2-(5-isoxazolyl)-phenol

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group.  Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4). Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A. 

Method for preparing 2-amino-n-(2,2,2-trifluoroethyl) acetamide

Method for preparing 2-amino-N-(2,2,2-trifluoroethyl) acetamide

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4). Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A. 

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Disclosed is a method for preparing a compound of Formula 1 comprising contacting a compound of Formula 2 with at least one compound of Formula 3 in the presence of a solvent comprising one or more organic solvents selected from ethers and nitriles and a catalytically effective amount of a palladium complex comprising at least one tertiary phosphine ligand of Formula 4 wherein Ris NHRor OR; Ris CHor Cl; Ris H, alkyl, cyclopropyl, cyclopropylmethyl or methylcyclopropyl; Ris H or C-Calkyl; Mis an alkali metal; and R, Rand Rare defined in the disclosure; provided that when Ris Cl, then X is Br. Also disclosed is a method for preparing a compound of Formula 5 wherein R, R, Rand Z are as defined in the disclosure using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the aforedescribed method. 

Process for preparing 2-amino-5-cyanobenzoic acid derivatives

Disclosed is a method for preparing a compound of Formula 1 comprising contacting a compound of Formula 2 with a metal cyanide reagent, a copper(I) salt reagent, an iodide salt reagent and at least one compound of Formula 3 wherein Ris NHRor OR; Ris CHor Cl; Ris H, C-Calkyl, cyclopropyl, cyclopropylcyclopropyl, cyclopropylmethyl or methylcyclopropyl; Ris H or C-Calkyl; Y is Br or Cl; X is NRor O; n is 0 or 1; and R, R, R, R, R, R, R, Rand Rare as defined in the disclosure. Also disclosed is a method for preparing a compound of Formula 2 wherein Y is Br and Ris NHRcomprising introducing a gas containing bromine into a liquid containing a compound of Formula 4, and further disclosed is a method for preparing a compound of Formula 5 wherein R, R, Rand Z are as defined in the disclosure using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the method disclosed above. 

A process for preparing phenserine compounds which are known acetylcholinesterase inhibitors from physostigmine compounds by hydrolysis to form an eseroline compound which is then condensed with an isocyanate.

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Wilmington, DE, United States of America

Joerg Bruening