Hoffmann-la Roche Inc.

Joseph Foricher

Rudolf Schmid

Bernd Heiser

Patrizio Mattei

Emil A Broger

Ulrich Zutter

Jean-Michel Adam

Bruno Lohri

Marco Cereghetti

Alec Fettes

Karlheinz Pfoertner

Stefan Abrecht

Gerard Moine

Claude Furbringer

This invention relates to a process of the preparation of the novel intermediate (S)-4-fluoromethyl-dihydro-furan-2-one of the formula and with its use for the manufacture of pyrido[2,1-a]isoquinoline derivatives of the formula which are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

Process for the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one useful in the preparation of the DPP-IV inhibitor (S)-1 ((2S,3S,11bS)-2-amino-9,10-dimethoxy-1,3,4,6,7, 11b-hexahydro-2H-pyrido[2,1-a] isoquinolin-3-yl)-4-fluoromethyl-pyrrolidin-2-one

A process for the manufacture of bisphosphine oxide compounds and bisphosphonates as intermediates for the production of bisphosphine ligands, in which in a single step process

Process for the manufacture of bisphosphine oxide and bisphosphonate

.alpha., .beta.-Unsaturated acids of the formula ##STR1## wherein R.sup.1 signifies C.sub.1 -C.sub.5 -alkyl and Ar signifies an aryl group which is optionally substituted by one or more substituents selected from the group consisting of halogen, phenyl, C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.5 -alkoxy, perfluorinated C.sub.1 -C.sub.5 -alkyl or perfluorinated C.sub.1 -C.sub.5 -alkoxy can be obtained from new or known compounds of the formula ##STR2## Compounds I can be converted by asymmetric hydrogenation into corresponding optically active saturated acids.

Process for making .alpha.,.beta.-unsaturated carboxylic acids

Novel chiral phosphorus compounds of the formula ##STR1## wherein R signifies lower alkyl, R.sup.1 signifies phenyl and R.sup.2 and R.sup.3 signify hydrogen or lower alkoxy, which are suitable in the form of complexes with a metal of Group VIII as catalysts for asymmetric hydrogenations and for enantioselective hydrogen displacements in prochiral allylic systems.

Chiral phosphorus compounds

Phosphorus compounds

Chiral phosphines

Chirale phosphines

The invention is directed to a process for the catalytic oxidation of an isoprenoid containing at least one allylic hydrogen atom, which process comprises reacting the isoprenoid with oxygen or an oxygen-containing gas in an inert solvent in the presence of a N-hydroxydicarboxylic acid imide of the formula ##STR1## wherein A-B stands for CH.sub.2 -CH.sub.2, CH.dbd.CH, an aromatic hydrocarbon residue or a group derived from one of these groups in which one or more hydrogen atoms is/are replaced by alkyl or halogen, to produce a primary of secondary hydroperoxide. The process of the invention is suitable for the manufacture of steroids, vitamins, odorant substances, carotinoids and the like.

Process for the catalytic oxidation of isoprenoids having allylic groups

Growing community of inventors

Mulhouse, France

Joseph Foricher