Lonza Ag

Lonza Inc.

Hanspeter Mettler

John McGarrity

Dominique Michel

Walter Brieden

Martin Clausen

Paul Hanselmann

Colette Mettler, Legal Representative

John Mcgarrity

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.

A process for the preparation of formylimidazoles of the general formula: or its tautomers, in which R.sup.1 is hydrogen or alkyl, and R.sup.2 is hydrogen, halogen or alkyl. In a first stage, an imidazole derivative of the general formula: ##STR1## or its tautomers, in which R.sup.1 and R.sup.2 are as defined above, is converted, by introducing an amino protective group, into an imidazole derivative of the general formula: ##STR2## or its tautomers, in which R.sup.3 is an amino protective group. Such derivative is formylated in a second stage in the presence of an organometallic compound and a suitable electrophile to give an imidazole derivative of the general formula: ##STR3## or its tautomers, in which R.sup.1, R.sup.2 and R.sup.3 are as defined above. Then, in a third stage, the end product of the formula I is obtained by cleaving off the amino protective group.

Process for the preparation of formylimidazoles

Process for the production of aminomalonic acid dinitrile salts from malonic acid dinitrile by the hydrogenation of its oximation product.

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Visp, Switzerland

Hanspeter Mettler