Process for the preparation of N-(4-piperidinyl)-N-ethyl-phenylacetamides from N-Boc-4-oxopiperidine

A process for the preparation of an N-(4-piperidinyl)-N-ethyl-phenylacetamide of formula (I):

• wherein R1 is S(O)2(C1-4 alkyl), and R2 is hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy, cyano or S(O)2(C1-4 alkyl);
• the process comprising the steps of:
• a. hydrogenating a mixture of ethylamine and a compound of formula (II) (1-tert-butoxycarbonyl-4-piperidone):
• in a solvent comprising ethanol, in the presence of a suitable palladium or platinum catalyst, at a pressure in the range 1-5 bar and at a temperature in the range 10-80° C., to form a compound of formula (III) (1-tert-butoxycarbonyl-4-(N-ethylamino)piperidine):
• b. reacting a compound of formula (IV):
• with carbonyldiimidazole in an ether or an aromatic solvent, at a temperature in the range 10-80° C.;
• and reacting the product so formed with the compound of formula (III) at a temperature in the range 10-80° C. in a suitable solvent, to form a compound of formula (V):
• and,
• c. forming a compound of formula (I) by treating a compound of formula (V) with HCl in a suitable solvent, at a temperature in the range 10-80° C.