Dimethylformamide → (S)-2-amino-4'-fluoro-7'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

Participants

Reaction Conditions

Reaction Steps

A 500 mL RBF was charged with (S)-2-amino-7′-bromo-4′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (20.00 g, 54.8 mmol), 2-fluoropyridin-3-ylboronic acid (13.89 g, 99 mmol) and sodium carbonate (23.22 g, 219 mmol). DMF (130 mL) was added and the mixture was stirred for 1 minute before tetrakis(triphenylphosphine) palladium (4.43 g, 3.83 mmol) and water (52.2 mL) were added. The mixture was capped with argon, equipped with a reflux condenser and heated at 85° C. for 16 hrs. The mixture was cooled to room temperature and the resulting yellow precipitate was filtered. The filtrate was diluted with water (200 mL) and saturated ammonium chloride (200 mL), leading to the formation of a white precipitate and a brown semisolid. The precipitate was filtered and the semisolid was triturated with water (˜200 mL) to provide a brown solid which was also filtered and washed with water. The combined solids were washed excessively with water and dried overnight under a stream of air to afford (S)-2-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol as tan solid which was used without further purification.

Provenance & Evidence