Water → HCID 68288764, compound

Participants

Reaction Conditions

Reaction Steps

To a 80 mL microwave vessel containing the compound prepared in Example 15 (263.9 mg) was added Na2CO3 (181.7 mg) and Pd(PPh3)4 (48.8 mg). The 4-(3-bromo-2-fluorophenoxy)tetrahydro-2H-pyran (253.6 mg) was added by dissolving in 3:1 1,4-dioxane:H2O then adding via pipet and using the remainder of the solvent to wash over any remaining material (total volume: 8.5 mL). The mixture was stirred and sparged with argon for 5 minutes. The vial was placed in the microwave then heated to 150° C. After 15 minutes at 150° C., the mixture was allowed to cool. The dark brown mixture was diluted with EtOAc and washed with H2O two times. The aqueous layers were back extracted with EtOAc. The combined organic layers were washed with brine then dried over Na2SO4, filtered and solvent was removed in vacuo. The material was absorbed onto silica and purified on the Isolera (50 g silica column; 0-15% MeOH in EtOAc) followed by purification via reverse phase on the Isolera (60 g C18 column; 5-95% ACN with 0.1% trifluoroacetic acid (TFA) in H2O with 0.1% TFA). Fractions containing product were combined and solvent was removed in vacuo. The material was taken up in MeOH and desalted by passing through a StratoSphere 200 mg PL-HCO3 MP SPE cartridge. Resin was washed with MeOH and 20% MeOH in DCM. Solvent was removed in vacuo to give the title compound (94.9 mg) having the following data as a dark amber solid/film solid.

Provenance & Evidence