Process for the production of ozanimod

A process for preparing a compound of formula (I) or an acid addition salt of said compound of formula (I)

• comprising
• removing a protective group or protective groups in an organic solvent and an acidic medium
• from
• a) a compound of formula (IV)
• in which R represents a protective group selected from the group consisting of substituted methyl ether groups, tetrahydropyranyl groups, substituted ethyl ether groups and silyl ether groups serving as temporary protection of the hydroxyl group on the compound of formula (I), wherein the oxygen residue of the hydroxyl group together with a silyl group forms the silyl ether group,
• or
• b) a compound of formula (V)
• or
• c) a mixture of the compound of formula (IV) and the compound of formula (V), and
• optionally transforming the compound of formula (I) into an acid addition salt, and
• wherein the compound of formula (IV) or the compound of formula (V) have been prepared from of a compound of formula (III), (II) or (III/A),
• and
• wherein a compound of formula (III)
• in which R represents a protective group selected from the group consisting of substituted methyl ether groups, tetrahydropyranyl groups, substituted ethyl ether groups, and silyl ether groups, wherein the oxygen residue of the hydroxyl group together with a silyl group forms the silyl ether group,
• has been produced from a compound of formula (VT)
• and a compound of formula (II) is not isolated
• in which R represents a protective group selected from the group consisting of substituted methyl ether groups, tetrahydropyranyl groups, substituted ethyl ether groups, and silyl ether groups, wherein the oxygen residue of the hydroxyl group together with a silyl group forms the silyl ether group;
• or
• wherein the compound of formula (II) is produced in a reaction mixture, wherein a reaction mixture containing dimethylformamide and surplus alkylating agent is extracted with a mixture of water and an ester solvent, and an oil obtained by evaporating an ethyl acetate phase is, without further purification, dissolved in an alcohol solvent, and then reacted with hydroxylamine in presence of a base;
• or
• wherein a compound of formula (III/A)
• is produced from the compound of formula (VI), an alkylating agent that is (2-bromoethoxy)-t-butyldimethylsilane, and a base that is sodium hydride, to give an obtained compound of formula (II/A)
• which is then dissolved in an alcohol solvent, and reacted with hydroxylamine hydrochloride in presence of a base to give the compound of formula (III/A).