Phthalimide → tert-butyl (2S)-2-[5-(4-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]-phenoxymethyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

Phthalimide (480 mg) was added to a solution of tert-butyl (2S)-2-(5-[4-(hydroxymethyl)phenoxymethyl]-1,2,4-oxadiazol-3-yl)-1-piperidinecarboxylate [see Preparation 13] (1.06 g) in tetrahydrofuran (10 ml). The mixture was cooled to 0° C. and triphenylphosphine (1.07 g) was added followed by diethylazodicarboxylate (0.642 ml). The resulting yellow solution was stirred at 0° C. for 10 mins. and then at room temperature for 1 hour. The mixture was evaporated to a low volume under reduced pressure and partitioned between dichloromethane and water. The organic layer was separated, washed with brine, dried over magnesium sulphate and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 90:10 changing to 70:30, by volume, hexane:ethyl acetate to afford tert-butyl (2S)-2-[5-(4-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]phenoxymethyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylate (1.09 g) as a white solid.

Provenance & Evidence