Sodium Bicarbonate → 2-Fluoro-9-oxo-9,10-dihydroacridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask containing polyphosphoric acid (254 g) at 165-172° C. was added finely ground compound 174D (15.0 g, 55.6 mmol) over 30 min. After the addition was complete, the reaction mixture was stirred for 10 min at 165° C. HPLC indicated that the reaction was complete. While at 165° C., the mixture was slowly added to a mixture of ice and sodium bicarbonate. The pH was adjusted to 3.0 with additional solid sodium bicarbonate, and the resulting mixture was filtered through a medium porosity fritted funnel to give a greenish-yellow paste which was washed with water (3×) and air-dried under vacuum. The resulting paste was rinsed with MeOH into a flask. The paste/MeOH mixture was then sonicated to disperse the paste. DCM was added, and the mixture was concentrated under reduced pressure. The azeotrope procedure was repeated 2× to give 12.0 g (84%) of acridone acid 174E as a yellow solid. HPLC retention time=2.35 min. (Condition A) and LC/MS M+1=258.03. 1H-NMR (500 MHz, DMSO) δ 7.30 (t, 1H, J=7.6 Hz), 7.56 (d, 1H, J=7.6 Hz), 7.78 (t, 1H, J=7.6 Hz), 7.93 (d, 1H, J=11.0 Hz), 8.11 (d, 1H, J=6.1 Hz), 8.22 (d, 1H, J=7.6 Hz), and 12.06 (s, 1H).

Provenance & Evidence