A mixture of tert-butyl methyl((2S)-1-oxo-1-(4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)propan-2-yl)carbamate (156 mg, 360 μmol), 3-(bromomethyl)benzo[d]isoxazole (83.9 mg, 396 μmol), Cs2CO3 (141 mg, 432 μmol) and NaI (64.7 mg, 432 μmol) in DMF (900 μL) was stirred at RT for 18 h, diluted with EtOAc, washed with H2O, brine, dried over Na2SO4, filtered, and the filtrate concentrated to give a residue that was purified by silica gel chromatography. The resulting material was purified by supercritical fluid chromatography (SFC) to provide tert-butyl (S)-1-((S)-5-(benzo[d]isoxazol-3-ylmethyl)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (54.5 mg, 27%) as a white foam.
