A Review of U.S.Patents in the Field of Organic Process Development Published during November and December 2004

摘要

The selection of 20 patents summarised in this review is from an original list of 223 that fitted the original criteria,and it is hoped that there is something to stimulate readers.The control of exothermic reactions is critical in improving the selectivity in many reactions.The rate of removal of heat is the key factor yet is often a limitation on a plant scale and can be forgotten by chemists in the laboratory.This can be done by a number of methods,and there are two patents in this selection that address this issue.One uses a solvent as a heat sink in the synthesis of an intermediate for salmeterol.The second solves the problem by changing the order of addition of the reactants in the preparation of a neurokinin-1 receptor antagonist.An improved process for the stereoselective formation of 1,3-diols by catalytic hy-drogenation of ketones is described that simply involves the addition of magnesium salts to the catalyst.This improves conversion and the ratio of syn and anti isomers.A novel range of seleno compounds that are prepared from nitrones is described that could be useful in treating brain cell decay.Fluorinated derivatives are important intermediates in many areas,and a number of patents cover such compounds.A novel process for preparing an intermediate for liquid crystals that contains a CF_3 group is described.Previous commercial routes did not use fluorinated starting materials,but the new method uses a readily available compound already containing the CF_3 group.One patent claims a method for making fluorinated ketones using TFA,but it is carried at > 280 deg C and hence is limited to relatively low-molecular-weight,thermally stable compounds.A method of preparing fluoro-isocyanates from the chloro derivatives using HF is described although the actual fluorination appears to proceed via carbamoyl fluorides.These are formed as intermediates in the reaction.The production of flavours and fragrances is an important industry,and one patent reports on an improved method for making carvone and carveol by selective rearrangement of limonene oxide using metal oxides and phenolic activators.As older male readers will be aware,the incidence of prostate problems increases with age.Hence,these readers may be interested in an improved method for the production of tamulosin,a drug used in treating enlarged prostate.Some of the patents describe improvements or new methods for making established drugs often because the original patents have expired.However,the inclusion of a patent in this review does not imply any legal or commercial significance.It is worth reiterating that patents do contain physical property and spectroscopic data that may not be published elsewhere.Some patents describe experiments involving the production of tens if not hundreds of kilograms,and it can be surmised that such processes are in advanced stages of development.The advantages listed for any patent are those claimed by the assignees unless this reviewer has prior knowledge.