Process for preparing (r)-2-amino-3-phenylpropyl carbamate

A process for preparing (R)-2-amino-3-phenylpropyl carbamate, compound of formula (I), or a pharmaceutically acceptable acid addition salt thereof

• the process comprising the steps of:
• a) providing a mixture comprising nitrogen-protected (R)-2-amino-3-phenylpropan-1-ol, compound of formula (III)
• wherein P is a N-protecting group selected from carbobenzyloxy (Cbz), p-methoxybenzyl (PMB), and 3,4-dimethoxybenzyl (DMPM), and
• an alkali metal cyanate in an amount of 1.0 to 1.8 molar equivalents with respect to compound of formula (III), in the presence of a solvent,
• b) adding an acid with a pKa measured in water at 25° C. lower than 1.0 in an amount of 1.5 to 3.5 molar equivalents with respect to the alkali metal cyanate to the mixture of step (a), at a temperature from 0° C. to 10° C., to provide O-carbamoyl-N-protected-(R)-2-amino-3-phenylpropan-1-ol, compound of formula (II), wherein P is as defined above,
• c) adding at least one portion of an alkali metal cyanate wherein each portion is used in an amount of 0.1 to 0.3 molar equivalents with respect to compound of formula (III) to the mixture of step (b), at a temperature from 0° C. to 10° C.,
• d) removing the N-protecting group from the compound of formula (II) to give O-carbamoyl-(R)-2-amino-3-phenylpropan-1-ol, compound of formula (I),
• e) optionally, converting the compound of formula (I) into a pharmaceutically acceptable acid addition salt thereof.