Hydrochloric Acid → (+/-)-2-(3-Chloro4-fluoro-phenylamino)-N-[2-methyl-5-(piperidin-4-yloxy)-phenyl]-acetamide, dihydrochloride

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3-chloro-4-fluoro-phenylamino)-N-(5-hydroxy-2-methyl-phenyl)acetamide (0.10 g) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (Synlett. 1998, 4, 379) (0.163 g) in tetrahydrofuran (3 ml) was added tributylphosphine (0.20 ml) and 1,1′-(azodicarbonyl)dipiperidine (0.204 g) and the mixture heated at 60° C. for 3 hours. Further 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.163 g), tributylphosphine (0.20 ml) and 1,1′-(azodicarbonyl)dipiperidine (0.204 g) were then added and the heating continued. After 3 hours, the reaction was cooled, poured into diethyl ether and filtered through Celite. After concentration, the residue was purified by NPHPLC (eluting with 0-5% ethanol in dichloromethane) to afford a white solid that was dissolved in methanol (3 ml) and HCl (2 ml of a 4M solution in dioxane) added. After 24 hours, the crystals were filtered off, washed with dichloromethane and dried in vacuo to give the title compound as a white powder (0.080 g).

Provenance & Evidence