N,N-Dimethylaniline → (4-Phenoxyphenyl) 4-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

A solution of 4-phenoxyphenol (30 g, 0.16 mol) and dimethylaniline (20.4 mL, 0.16 mol) in 200 mL of benzene plus 9 mL of dioxane was added dropwise over 1.5 hours under a nitrogen atmosphere to a solution of trichloromethyl chloroformate (9.7 mL, 0.08 mol) in 60 mL of benzene at ice bath temperature. After the addition, the cooling bath was removed and the stirring continued for 24 hours. The reaction mixture was filtered and the filtrate was then added dropwise under a nitrogen atmosphere to a solution of 4-hydroxypiperidine (16.3 g, 0.16 mol) and pyridine (26.1 mL, 0.32 mol) in 150 mL each of benzene, methylene chloride and tetrahydrofuran (THF) at ice bath temperature. After the addition, the reaction was stirred at ice bath temperature for 3 hours. The cooling bath was removed and the stirring continued overnight. The reaction mixture was diluted with benzene and washed with 1N HCl. The organic solution was separated, dried over anhydrous MgSO 4 and the solvent removed under reduced pressure to give 46.4 g of a yellow mushy solid. Purification by high pressure liquid chromatography (HPLC) with hexane: EtOAc mixtures gave 13.3 g of a white solid. Recrystallization from diisopropyl ether-methanol gave the title compound as a white crystalline solid (10.4 g, 21%), mp 128°-130° C.

Provenance & Evidence