This invention provides for a flow synthesis process for producing Oseltamivir and pharmaceutically acceptable salts thereof from shikimic acid in particular but not exclusively to a flow synthesis process for producing Oseltamivir phosphate from shikimic acid in a nine-step flow synthesis that provides for superior reaction times and product yields compared to known methods.

The present disclosure, in at least certain embodiments, is directed to shikimate (shikimic acid) analogues and compositions thereof, devices and kits which contain the shikimate analogues or compositions thereof, and methods of use of the compounds and compositions for treating and neutralizing irritant or odoriferous compounds on animate or inanimate surfaces or in atmospheres.

The present invention provides a method for producing a bifunctional compound having a norbornane skeleton, the method comprising a step of hydroformylating a compound having an olefin with carbon monoxide and hydrogen, wherein the molar ratio of the carbon monoxide to the hydrogen during the reaction is 55/45 or more and 95/5 or less in the hydroformylating step.

The present invention provides a method for producing a bifunctional compound having a norbornane skeleton, the method comprising a step of hydroformylating a compound having an olefin with carbon monoxide and hydrogen, wherein the molar ratio of the carbon monoxide to the hydrogen during the reaction is 55/45 or more and 95/5 or less in the hydroformylating step.

An object of the present invention is to provide a method for selectively producing a hydroxycarboxylic acid ester, the method including reducing a dicarboxylic acid monoester by means of a heterogeneous reaction. According to a method for producing a hydroxycarboxylic acid ester in an embodiment of the present invention, a hydroxycarboxylic acid ester represented by Formula (2) is produced by reducing a substrate dicarboxylic acid monoester represented by Formula (1) in the presence of a catalyst.

The catalyst comprises: metal species including M.sub.1 and M.sub.2; and a support supporting the metal species, and wherein M.sub.1 is rhodium, platinum, ruthenium, iridium or palladium; M.sub.2 is tin, vanadium, molybdenum, tungsten or rhenium; and the support is hydroxyapatite, fluorapatite, or hydrotalcite.

##STR00001##

An object of the present invention is to provide a method for selectively producing a hydroxycarboxylic acid ester, the method including reducing a dicarboxylic acid monoester by means of a heterogeneous reaction. According to a method for producing a hydroxycarboxylic acid ester in an embodiment of the present invention, a hydroxycarboxylic acid ester represented by Formula (2) is produced by reducing a substrate dicarboxylic acid monoester represented by Formula (1) in the presence of a catalyst.

The catalyst comprises: metal species including M.sub.1 and M.sub.2; and a support supporting the metal species, and wherein M.sub.1 is rhodium, platinum, ruthenium, iridium or palladium; M.sub.2 is tin, vanadium, molybdenum, tungsten or rhenium; and the support is hydroxyapatite, fluorapatite, or hydrotalcite.

##STR00001##

A compound (A) of the present invention is represented by the formula (1): wherein each R.sub.1 independently represents a group represented by the formula (2) or a hydrogen atom, and each R.sub.2 independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms, provided that at least one R.sub.1 is a group represented by the formula (2); and wherein -* represents a bonding hand.

The present invention provides a process for preparing a compound of the following general formula (2): wherein R.sup.1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, and R.sup.3 represents a hydrogen atom or a methyl group, the process comprising: subjecting a compound of the following general formula (1): wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, R.sup.3 represents a hydrogen atom or a methyl group, and the wavy bond represents an E-configuration, a Z-configuration, or a mixture thereof, to a Dieckmann condensation in the presence of base to form the compound (2).

##STR00001##

The present invention provides a process for preparing a compound of the following general formula (2): wherein R.sup.1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, and R.sup.3 represents a hydrogen atom or a methyl group, the process comprising: subjecting a compound of the following general formula (1): wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, R.sup.3 represents a hydrogen atom or a methyl group, and the wavy bond represents an E-configuration, a Z-configuration, or a mixture thereof, to a Dieckmann condensation in the presence of base to form the compound (2).

##STR00001##

A field of asymmetric catalytic synthesis, and in particular a preparation method for a high optical indoxacarb intermediate includes reacting 5-chloro-2-methoxycarbonyl-1-indanone ester (or indanone ester for short) with an oxidizing agent in the presence of a chiral Zr-salen polymer to obtain an indoxacarb intermediate (2S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indole-2-carboxylic acid methyl ester. The yield is stabilized between 86% and 90%, and the S-enantiomer content is up to 99%. Such catalyst can replace catalysts such as cinchonine, and greatly increase the content of the effective S-enantiomer of the indoxacarb, so that the content of the hydroxyl intermediate S-enantiomer of the indoxacarb is raised from 75% to 99% or more. In addition, the chiral Zr-salen polymer catalyst is recycled without retreatment, and can be recycled at least 5 times or more, greatly reducing the production cost and laying a foundation for the industrial production of high quality indoxacarb.