Tetrabutylammonium Fluoride Trihydrate → (S)-5-amino-4'-fluoro-2'-((3-methyloxetan-3-yl)ethynyl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-7'-ol

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with tetrabutylammonium fluoride trihydrate (0.301 g, 0.952 mmol), Pd(PPh3)4 (0.073 g, 0.063 mmol), and copper(I) iodide (12.3 mg, 0.065 mmol). The (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.241 g, 0.64 mmol) was added as a solution in THF (2.7 mL). Argon was blown through the vessel, and trimethyl((3-methyloxetan-3-yl)ethynyl)silane (0.161 g, 0.951 mmol) was added. The vessel was sealed and heated in an 80° C. oil bath for 1.5 h. The mixture was cooled and concentrated, diluted with water (15 mL), and the aqueous phase was extracted with 5% MeOH-DCM (3×25 mL). The organics were combined, washed with dilute brine (7 mL), dried over sodium sulfate and concentrated to afford (S)-5-amino-4′-fluoro-2′-((3-methyloxetan-3-yl)ethynyl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol, which was used in the next step without further purification.

Provenance & Evidence