Dsm IP Assets B.v.

Hoffmann-la Roche Inc.

Roche Vitamins Inc.

Reinhard Karge

Werner Bonrath

Jing Chang Huang

Thomas Netscher

Ulla Letinois

Jan Schütz

Jocelyn Fischesser

Felix Roessler

Shuping Jing

Ralf Proplesch

Horst Pauling

Michael Schneider

Lisa Giraudi

Andrew George Gum

Wolfgang Hölderich

Ralph Haerter

Valerie Enjolras

Ralf Keuper

Gerhard Shiefer

Helmut Fritsch

Jan Schultz

Yann Pressel

Erhard Henning Fleischhauer

Bernhard Markus Ernst Russbüldt

Verena Ritzerfeld

Jan SCHÜTZ

Gerhard Schiefer

The present invention relates to a novel process for the manufacture of Grewe-diamine comprising the following step: hydrolyzing a compound of formula (II), wherein R is hydrogen or straight- or branched chain C1-4 alkyl, with an aqueous alkali or alkaline-earth metal hydroxide solution, characterized in that the hydrolysis is carried out in the presence of an organic solvent.

Process for the manufacture of a precursor of vitamin B1

Use of pure lanthanum oxide which is obtained by calcination of oxygen-containing lanthanum salts at temperatures of at least 700&#xb0; C. as heterogeneous catalyst in the aldol condensation of citral and acetone to give pseudoionone, and process for the preparation of pseudoionone by aldol condensation of citral and acetone in the liquid phase using pure lanthanum oxide.

Process for preparing pseudoionone

Isomerization of &#x3b2;-keto-allenes of the general formula I wherein Ris hydrogen, methyl or ethyl, in particular hydrogen or methyl; Ris hydrogen or methyl; Ris hydrogen or methyl, in particular methyl and Ris an aliphatic hydrocarbon residue containing 1-37 carbon atoms, into corresponding &#x3b1;,&#x3b3;-dienones of formula II by treatment with a basic ion exchange resin. 

Isomerization of &#x3b2;-keto-allenes

A process for the preparation of 5-substituted 4-amino-2-methylpyrimidines of the formula wherein R is CONHor CN, and of acid addition salts thereof, characterized in that a compound of formula HN&#x2014;CH&#x2550;C(R) CN (II) is reacted with acetimidic acid methyl ester or an acid addition salt thereof and that, if desired, a compound of formula I is transferred into an acid addition salt, and the transformation of a compound of formula II wherein R is CONHinto a compound of formula II wherein R is CN by treatment with POCl.

Process for the preparation of pyrimidine derivatives

A process for the preparation of 5-substituted 4-amino-2-methylpyrimidines of the formula (I) wherein R is CONHor CN, and of acid addition salts thereof, characterized in that a compound of formula HN CH&#x2550;C(R)CN (II) is reacted with acetimidic acid methyl ester or an acid addition salt thereof and that, if desired, a compound of formula (I) is transferred into an acid addition salt, and the transformation of a compound of formula (II) wherein R is CONHinto a compound of formula (II) wherein R is CN by treatment with POCI. 

The present invention is directed to a process for the manufacture of compounds of formula IV wherein Ris an amino protecting group, and Ris hydrogen or Calkyl, comprising a) reacting a compound of formula Ia, wherein Mis a cation, preferably selected from the group consisting of Li, Na+, K, &#xbd; Mgand &#xbd; Zn, (formula 1) with an ammonium salt NHX, wherein Xis an anion, preferably selected from the group consisting of chloride, bromide, sulfate and acetate, in a solvent to a compound of formula II b) reacting a compound of formula II with a nitrile R&#x2014;CN in the presence of a base to a compound of formula IV. The present invention is further directed to compounds of formula II and their use for the manufacture of vitamin B. 

Synthesis of substituted 4-amino-pyrimidines

Process for the manufacture of a compound of the structure (I) with R=hydrogen, alkyl (C1-C10, linear, cyclic or branched, aliphatic or aromatic), NR'R&#x2033; (wherein R&#x2032; and R&#x2033; are independently selected from H, alkyl [C1-C10, linear, cyclic or branched, aliphatic or aromatic] and R=CHRwherein Ris selected from NHR1&#x2032;&#x2033; (with R&#x2032;&#x2033;=C(O)H, C(O)CH, C(O)alkyl, CHCH(OMe)or other saponifiable residues), alkyl (C1-C10, linear, cyclic or branched) aromatic residues, heteroaryl residues, substituted aryl residues, e.g. 3,4,5-trimethoxy-phenyl) wherein 1 equivalent of an &#x3b1;-formyl-propionitrile salt is reacted with 0.75 to 2 equivalents of an acetamidine salt in the presence of a Lewis acid. 

Synthesis of 4-amino-pyrimidines scaffolds

The invention relates to an improved process for the manufacture of substitute 2-cyanocinnamic esters. This novel economical process provides products in high purity and yields.

Process for the manufacture of substituted 2-cyano cinnamic esters

The invention relates to an improved process for the manufacture of substituted 2-cyanocinnamic esters. This novel economical process provides products in high purity and yields.

The present invention relates to a process for the manufacture of cyclic thio esters (thiolactones) and related compounds by hydrogenation of cyclic thioanhydrides in the presence of metal catalysts.

Manufacture of thiolactones

The present invention relates to a process for the manufacture of cyclic monocarboxylic esters (lactones) and related compounds by hydrogenation of cyclic dicarboxylic acid anhydrides in the presence of metal catalysts.

Manufacture of lactones

A process for manufacturing a 3-unsubstituted, 3-monosubstituted or 3,3-disubstituted 9-acyloxy-1,5-dihydro-8-methylpyrido[3,4-e] [1,3]dioxepin (I) and optionally for manufacturing pyridoxine involves performing an addition reaction between a 4-methyl-5-alkoxy-oxazole (II) and a 2-unsubstituted, 2-monosubstituted or 2,2-disubstituted 4,7-dihydro-(1,3)-dioxepin (III) in the substantial absence of a solvent and a catalyst to give a product mixture consisting essentially of the appropriate Diels-Alder adduct (IV) in a major proportion and the appropriate 3-unsubstituted, 3-monosubstituted or 3,3-disubstituted 1,5-dihydro-8-methylpyrido[3,4-e] [1,3]dioxepin 9-ol (V) in a minor proportion, removal of a substantial proportion of the unreacted oxazole and dioxapin starting materials from the product mixture by distillation under reduced pressure, addition of a substantially anhydrous organic acid to said product mixture and rearrangement of the Diels-Alder adduct IV to further V in the presence of said substantially anhydrous organic acid with removal of the generated alkanol by distillation under reduced pressure, and acylation of the resultingly enriched quantity of V with an added carboxylic acid anhydride to produce the desired I, and optionally converting this so-manufactured acylation product I to pyridoxine by acid hydrolysis for achieving deprotection and deacylatiom. Pyridoxine is a well known form of vitamin Bwith well established utility.

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The present invention is a process for converting trimethylhydroquinone diacetate (TMHQ-DA) into trimethylhydroquinone-1-monoacetate (TMHQ-1-MA) by contacting TMHQ-DA with a lipase to effect an enzymatic monosaponification of the TMHQ-DA. Also provided are methods of making (all-rac)-&agr;-tocopherol and (all-rac)-&agr;-tocopherol acetate.

Process for the manufacture of a vitamin E intermediate

A process for the manufacture of 5-cyano-4-lower alkyl-oxazoles is described in which a 5-carbamoyl-4-lower alkyl-oxazole is dehydrated in an organic solvent under mild conditions with cyanuric chloride and an N,N-disubstituted-formamide.

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Staufen, Germany

Reinhard Karge