Dsm IP Assets B.v.

Astra Zeneca U.k. Limited

Basilea Pharmaceutica Ag

Dsm N.v.

Dsm Sinochem Pharmaceuticals Netherlands B.v.

Daniel Mink

Jacob Hermanus Mattheus Hero Kooistra

Hubertus Josephus Marie Zeegers

Joannes Maria Cornelis Antonius Mulders

Ben De Lange

Dennis Heemskerk

Michael Wolberg

Sven Panke

Mario Waser

Ruben Van Summeren

Harrie Vaessen

Andreas Hendrikus Maria De Vries

Johannes Gerardus De Vries

Anna Maria Cornelia Francisca Castelijns

Wilhelmus Hubertus Joseph Boesten

Friso Bernard Jan Van Assema

Peter Johannes Dominicus Maas

Joannes Gerardus Theodorus Kierkels

Peter Hans Riebel

Dominique Monique Charles Callant

Natascha Sereinig

David Hyett

Joannes Gerardus Kierkels

Franciscus Alphons Lommen

David John Hyett

The invention relates to a process for the manufacture of diastereomerically and enantiomerically enriched triazole compounds isavuconazole and ravuconazole, comprising a Reformatsky reaction between a ketone and a 2-halozincpropionate ester, followed by a resolution step, preferably an enzymatic resolution with an esterase enzyme.

Process for the manufacture of isavuconazole or ravuconazole

The present invention relates to a process for the preparation of a diol sulfone derivative comprising reaction of a halomethyl substrate with a thio-aryl compound to obtain a thio-ether compound, and oxidizing the thio-ether compound to the corresponding sulfone. In case of a chiral halomethyl substrate, the resulting chiral diol sulfone derivative is suitable as a building block for statin type compounds.

Process for the preparation of diol sulfones

The invention relates to the preparation of 2-(6-substituted-1,3-dioxane-4-yl)acetic acid derivatives of formula 1, where X stands for a leaving group, and R, R, and Reach independently stand for an alkyl group with 1-3 carbon atoms from 4-hydroxy-6-X-substituted-methyl-tetrahydropyran-2-one compounds, where X is as defined above, with the aid of an acetalization agent, in the presence of an acid catalyst. The invention also relates to the novel compounds of formula 1 as well as salts and acids to be prepared from these, with the ORgroup in formula 1 being replaced by an OY group, where X, Rand Rhave the meanings defined above and where Y stands for an alkaline (earth) metal or a substituted or unsubstituted ammonium group or stands for hydrogen, and to the novel compounds of formula 2. The products concerned are, after conversion into the t-butyl ester of 2-(6-hydroxymethyl-1,3-dioxane-4-yl)acetic acid, important as intermediary products in the preparation of statins.

Process for the preparation of 2-(6-substituted-1,3-dioxane-4-yl)acetic acid derivatives

The present invention relates to a process for the preparation of an enantiomerically enriched optionally substituted indoline-2-carboxylic acid or a salt thereof, wherein an enantiomerically enriched chiral ortho-X-substituted phenylalanine compound, wherein X is a leaving group, is subjected to cyclisation, preferably at a temperature of below about 140&#xb0; C., upon formation of the enantiomerically enriched indoline-2-carboxylic acid compound.

Process for the preparation of enantiomerically enriched indoline-2-carboxylic acid

Process for the preparation of 2-(6-substituted-1,3-dioxane-4-YL) acetic acid derivatives

The invention relates to a process for the preparation of a 2,4-dideoxyhexose or a 2,4,6-trideoxyhexose from a substituted or unsubstituted carbonyl compound with at least 2 carbon atoms and at least one &#x3b1;-hydrogen atom and a substituted or unsubstituted aldehyde in the presence of an aldolase and water, the reaction between the substituted or unsubstituted carbonyl compound with at least 2 carbon atoms and at least one &#x3b1;-hydrogen atom and the substituted or unsubstituted aldehyde being carried out at a carbonyl concentration of at most 6 moles/l of reaction mixture and the final concentration of the 2,4-dideoxyhexose or the 2,4,6-trideoxyhexose being at least 2 mass % of the reaction mixture. The invention also relates to the use of a 2,4-dideoxyhexose or a 2,4,6-trideoxyhexose obtained by means of a process according to the invention in the preparation of a medicine, particularly in the preparation of a statine.

Process for the preparation of 2,4-dideoxyhexoses and 2,4,6-trideoxyhexoses

The invention relates to a process for the preparation of (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile from 6-X-substituted-methyl-4-hydroxy-tetrahydro-pyran-2-one, wherein X stands for a leaving group, by reacting 6-X-substituted-methyl-4-hydroxy-tetrahydro-pyran-2-one with a cyanide ion in water and by subsequent lowering of the pH to a pH between 0 and 5. (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile and other compounds obtainable from (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile may suitably be used in the preparation of a pharmaceutical preparation, more in particular in the preparation of statins, more in particular in the preparation of Atorvastatine or a salt thereof, for instance its calcium salt. The invention also relates to (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile and other compounds obtainable therefrom.

Process for the preparation of (4-hydroxy-6-oxo-tetrahydropyran-2-yl) acetonitrile and derivatives

The invention relates to the preparation of 2-(6-substituted-1,3-dioxane-4-yl)acetic acid derivatives of formula (1), where X stands for a leaving group, and R, R, and Reach independently stand for an alkyl group with 1-3 carbon atoms from 4-hydroxy-6-X-substituted-methyl-tetrahydropyran-2-one compounds, where X is as defined above, with the aid of an acetalization agent, in the presence of an acid catalyst. The invention also relates to the novel compounds of formula (1) as well as salts and acids to be prepared from these, with the ORgroup in formula (1) being replaced by an OY group, where X, Rand Rhave the meanings defined above and where Y stands for an alkaline (earth) metal or a substituted or unsubstituted ammonium group or stands for hydrogen, and to the novel compounds of formula (2). The products concerned are, after conversion into the t-butyl ester of 2-(6-hydroxymethyl-1,3-dioxane-4-yl)acetic acid, important as intermediary products in the preparation of statins.

Process for the preparation of 2-(6-substituted-1,-3-dioxane-4-yl)acetic acid derivatives

Process for the preparation of (schiff bases of) &agr;-alkyl-&agr;-amino acid amides

Growing community of inventors

Eupen, Belgium

Daniel Mink