Formaldehyde → (S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

(S)-5-amino-2-(benzyloxycarbonylamino)pentanoic acid (10.0 g, 37.56 mmol) and ethyl 1,3-dioxoisoindoline-2-carboxylate (9.04 g, 41.28 mmol) in NMP (40.0 mL) were heated to 150° C. for 30 min in 4 microwave reaction tubes. The mixture was diluted with EtOAc (500 mL). The organic mixture was washed with water (100 mL×2) and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give an oil, which was redissolved in toluene. To the resulting solution were added paraformaldehyde, PTSA and molecular sieves (3 A) and the mixture was heated to 150° C. for 20 min in a microwave reactor. The reaction mixture was diluted with ether (800 mL), washed with NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel using a mixture of EtOAc and hexanes to give (S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate (11.6 g, 76% for 2 steps).

Provenance & Evidence