Potassium Acetate → (S)-5-amino-4'-fluoro-2'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-7'-ol

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with potassium acetate (6.14 mg, 0.063 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.77 mg, 2.504 μmol), and 2-fluoropyridin-4-ylboronic acid (4.23 mg, 0.030 mmol). The (S)-tert-butyl 2′-bromo-4′-fluoro-7′-hydroxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate (0.012 g, 0.025 mmol) was added as a solution in 1:1 acetonitrile/dioxane (1 mL). Water (0.1 mL) was added. Argon was blown through the vessel, which was then sealed and heated in a 100° C. oil bath for 6 h. The mixture was cooled, diluted with brine (10 mL), and the aqueous layer was extracted with 10% MeOH-DCM (3×20 mL). The organics were combined, washed with dilute brine (5 mL), dried over sodium sulfate and concentrated. The residue was purified by preparative TLC (20% MeOH in DCM) to afford 3.8 mg of (S)-5-amino-4′-fluoro-2′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol.

Provenance & Evidence