Dimethylformamide → Dimethyl 2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-2,4-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of dimethyl 4-(trifluoromethylsulfonyloxy)isophthalate T4.1 (39.00 g, 114 mmol) in DMF (228 mL, 114 mmol) at 23° C. was added 2-fluoro-5-methoxyphenylboronic acid (29 g, 171 mmol) (commercially available from Sigma-Aldrich, St. Louis, Mo., USA), and potassium carbonate (47 g, 342 mmol), followed by tetrakis(triphenylphosphine)palladium (9.2 g, 8.0 mmol). The mixture was heated to 90° C. and stirred for 18 hours. The reaction was cooled to room temperature. Water was then added to the reaction, and the resulting mixture was extracted with EtOAc. The combined organic layers were dried over MgSO4, and concentrated. The crude product was purified by silica gel flash chromatography (0-20% EtOAc/hexane) to afford dimethyl 2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-2,4-dicarboxylate T4.2 as a clear oil (32.00 g, 88% yield). MS ESI (pos.) m/e: 319.1 (M+H)+.

Provenance & Evidence