Process for the preparation of enantiomerically pure (5, 5′-dichloro-6,6′-dimethoxy-biphenyl-2,2′-diyl)- bis(diphenylphosphine oxides)

US6489513B2 · kind B2 · utility

Assignee

• BAYER HEALTHCARE LLC · DE

Inventors

• Torsten Pohl · Cambridge, US
• Thomas Prinz · Neunburg vorm Wald, DE
• Guido Giffels · Bonn, DE
• Wolfram Sirges · Düsseldorf, DE

Key dates

• Filing date: Nov 13, 2001
• Grant date: Dec 3, 2002
• Expiry date: Nov 13, 2021

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F9/5329
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The invention relates to the preparation of enantiomerically pure bis-diphenylphosphine oxides in a particularly advantageous manner by (1) reacting an aromatic bromine compound with a diphenylphosphinic chloride in a mixture of tetrahydrofuran and an aromatic hydrocarbon to give a diphenylphosphine oxide, which is isolated from a solution in an aromatic hydrocarbon by adding a saturated aliphatic hydrocarbon; (2) metalating the resulting diphenylphosphine oxide in the 6-position and reacting the metalated diphenylphosphine oxide with iodine at temperatures not less than −25° C. in such a way that a small amount of iodine is always present in excess, giving a 2-iodo-diphenylphosphine oxide; (3) preparing a racemic bis-diphenylphosphine oxide from the resulting 2-iodo-diphenylphosphine oxide using copper and an aromatic hydrocarbon solvent and crystallizing the racemic bis-diphenylphosphine oxide from a solution in an aromatic hydrocarbon; and (4) separating isomers using an enantiomerically pure mono- or dicarboxylic acid to obtain a first enantiomer by crystallization from a solution in an aromatic hydrocarbon and obtaining a second enantiomer by hydrolysis and subsequen…