Johnson Matthey Public Limited Company

Astrazeneca Ab

Maureen Young

George Scott Wilson

Nicolas Archer

Melville Mitchell

Neil John Goodwin

Amy Price

Neil Kenneth Thomson

Timothy Davies

Saroop Matharu

Andrew D Jones

Brian Heinrich

Ewart Grant

Jonathan David Moseley

Evan William Snape

Ian Patel

Michael Bease

Barbara Jamieson

The present invention provides processes for preparing morphinan-6-one compounds, in particular oxymorphone and salts thereof, having improved impurity profiles.

Process for the preparation of morphinan-6-one compounds

The present invention provides a process for preparing an oxycodone acid adduct, said process comprising hydrogenating an aqueous solution of 14-hydroxycodeinone and an acid to form a solution of the oxycodone acid adduct, wherein the hydrogenation is carried out at one or more temperatures greater than ambient temperature in the presence of a hydrogenation catalyst and hydrogen gas, wherein the solution of oxycodone acid adduct comprises 6&#x3b1;-oxycodol in an amount &#x2266;about 0.800 area % as determined by HPLC.

Process

A process for the reduction of a 6-keto group in a morphinan alkaloid to the corresponding 6-hydroxy group includes hydrogenating the 6-keto group using gaseous hydrogen in the presence of a heterogeneous catalyst and a solvent, to yield the 6-hydroxy morphinan alkaloid, wherein the reduction is carried out at a pH in the range of about 5 to about 7, and the 6-hydroxy morphinan alkaloid has an &#x3b1;:&#x3b2; ratio of &#x3e;85:15.

Process for reducing the 6-keto group of a morphinan alkaloid to the 6-hydroxy group by hydrogenation

A process for preparing a compound of formula (A), (B) or (C): wherein P is H, CHor a hydroxyl protecting group; X is O, a protected ketone, OH, a protected hydroxyl group or H; Y is OH, a protected hydroxyl group or H; W is C(CH)OH, C(CH)(C(CH))OH or COCH; Z is C-Calkyl or C-Carylalkyl; andis a single bond or a double bond, is disclosed. The process is a reductive alkylation in the presence of hydrogen and a reductive alkylation catalyst.

Preparation of opiate analgesics by reductive alkylation

A process for preparing a compound of formula (A), (B) or (C): wherein P is H, CHor a hydroxyl protecting group; X is O, a protected ketone, OH, a protected hydroxyl group or H; Y is OH, a protected hydroxyl group or H; W is C(CH)OH, (CH)(C(CH))OH or COCH; Z is C-Calkyl or C-Carylalkyl; andis a single bond or a double bond, is disclosed. The process includes reductive alkylation in the presence of hydrogen and a reductive alkylation catalyst.

Process for preparing 3-[(4S)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydroquinolin-4-yl]benzonitrile, pharmaceutical compositions containing the compound and methods of treatment using the same.

Method

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Edinburgh, United Kingdom

Maureen Young