Lonza Ag

Lonza Inc.

Dominique Michel

John McGarrity

Hanspeter Mettler

Walter Brieden

Rudolf Fuchs

Martin Clausen

Paul Hanselmann

Colette Mettler, Legal Representative

John Mcgarrity

A process is disclosed for the preparation of a compound of formula and/or an addition salt of a proton acid, wherein Rand Rindependently represent alkyl, cycloalkyl, aryl or aralkyl, each aryl or aralkyl being optionally further substituted with alkyl, alkoxy and/or halogen.

Process for the preparation of N-monosubstituted &#x3b2;-amino alcohols

A process is disclosed for the preparation of a compound of formula and/or an addition salt of a proton acid, wherein Rand Rindependently represent alkyl, cycloalkyl, aryl or aralkyl, each aryl or aralkyl being optionally further substituted with alkyl, alkoxy and/or halogen. The process involves reacting a mixture comprising a methyl ketone of formula and a compound of formula HN&#x2014;R(V) and/or an addition salt of proton acid, and formaldehyde in the presence of a solvent selected from the group consisting of water, aliphatic alcohols, cycloaliphatic alcohols and mixtures thereof, and optionally a proton acid to afford a &#x3b2;-amino ketone of formula and/or an addition salt of a proton acid, and reducing the carbonyl group of said &#x3b2;-amino ketone to afford a compound of formula I, and/or an addition salt of a proton acid

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A process for the preparation of N-monosubstituted &#x3b2;-aminoalcohol sulfonates of formula (1a), (1b): wherein Ris C-aryl or C-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C-alkyl or C-alkoxy groups, Ris C-alkyl or C-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C-alkyl or C-alkoxy groups, and wherein Ris selected from the group consisting of C-alkyl, C-cycloalkyl, C-aryl and C-aralkyl residues; including a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, said organic solvent which can include water to provide N-monosubstituted &#x3b2;-aminoketone sulfonates of formula (II): wherein R, Rand Rare as defined above, and b) asymmetrically hydrogenating.

Process for the preparation of enantiomerically pure 1-substituted-3-aminoalcohols

A process for the preparation of N-monosubstituted &#x3b2;-aminoalcohol sulfonates of formula (Ia), (Ib): wherein Ris C-aryl or C-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C-alkyl or C-alkoxy groups, Ris C-alkyl or C-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C-alkyl or C-alkoxy groups and wherein Ris selected from the group consisting of C-alkyl, C-cycloalkyl, C-aryl and C-aralkyl residues. The process has the steps of (a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, the organic solvent optionally containing water, to afford N-monosubstituted &#x3b2;-aminoketone sulfonates of formula (II): wherein R, Rand Rare as defined above, and (b) asymmetrically hydrogenating. The sulfonates in the presence of a base and a catalyst of a transition metal and a disphosphine ligand, in a polar solvent, optionally in the presence of water.

A salt of a carboxylic acid with an aminoketone of formula II.

A salt of a carboxylic acid with an aminoalcohol of formula I.

A process for the preparation of enantiomerically pure 1-substituted-3-amino-alcohols, particularly of (S)-(&#x2212;)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of the formula: wherein Ris 2-thienyl, 2-furanyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C-alkyl or C-alkoxy groups, and wherein Ris C-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C-alkyl or C-alkoxy groups. The corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Salts of a carboxylic acid with the aminoketones and the aminoalcohols obtained by asymmetrically hydrogenating the aminoketones, respectively.

Ethynylcyclopropane is prepared from (1,1-dimethoxyethyl)cyclopropane by a two-stage elimination of methanol. Ethynylcyclopropane is an intermediate in the synthesis of pharmaceutically active ingredients, for example, antiviral agents.

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Sierre, Switzerland

Dominique Michel