Hydrochloric Acid → (Rac)-2'-(3,3-dimethylbut-1-ynyl)-7'-(pyrimidin-5-yl)-5h-spiro[oxazole-4,9'-xanthen]-2-amine

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with (racemic)-2′-Chloro-7′-(5-pyrimidinyl)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (100 mg, 274 μmol), cesium carbonate (134 mg, 411 μmol), bis(triphenylphosphine)palladium(II) chloride (19 mg, 27 μmol) and tri-tert-butylphosphonium tetrafluoroborate (16 mg, 55 DMF (1 ml), DBU (21 μl, 137 μmol) and 3,3-dimethylbut-1-yne (167 μl, 1371 μmol) were added. The vial was sealed and heated at 150° C. in Biotage microwave oven for 60 min. The mixture was diluted with 5 ml of EtOAc, filtered through Celite and concentrated in vacuo to give brown oil, which was re-dissolved in 7 ml of EtOAc and shaken with 10 ml of 2N HCl. Acidic aqueous layer was basified with 30% ammonium hydroxide and precipitated brown oil was extracted twice with EtOAc. The organic layers were washed with brine, concentrated, dissolved in 1.5 ml of DMF, filtered through Nalgene PTFE 0.2 mkm filter and subjected to preparative reverse phase HPLC (15-90% ACN in 0.1% aq TFA). The fractions containing product were concentrated in vacuo in order to remove ACN, saturated NaHCO3 was added and the mixture was extracted with EtOAc (15 ml). The organic layer was washed with brine, dried over MgSO4 and concentrated to give (rac)-2′-(3,3-dimethylbut-1-ynyl)-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (49% yield).

Provenance & Evidence