1,2-Dimethoxyethane → 3'-Chloro-2-fluoro-6-methoxy-3-(4-nitro-benzyl)-biphenyl

Participants

Reaction Conditions

Reaction Steps

In a 40 mL vial equipped with a stir bar was placed 3-bromomethyl-3′-chloro-2-fluoro-6-methoxy-biphenyl (I-33, 400 mg, 1.21 mmol), 4-nitrophenylboronic acid (420 mg, 1.45 mmol), potassium phosphate (tribasic) (514 mg, 2.42 mmol), dimethoxyethane (3.5 mL) and 50% aqueous ethanol (3.5 mL). After degassing with nitrogen for 15 minutes, tetrakis(triphenylphosphine)palladium(0) (140 mg, 0.121 mmol) was added. The mixture was heated to 60° C. for 18 hours and then the palladium catalyst was removed by filtering through Celite. To the filtrate were added water (50 mL) and a saturated ammonium chloride solution (50 mL). After extracting with ethyl acetate (3×50 mL), the organic portions were combined, washed with brine (75 mL), dried (MgSO4) and concentrated. The crude material was purified by silica gel chromatography utilizing 20% ethyl acetate/hexanes as eluent to produce 342 mg (76%) of 3′-chloro-2-fluoro-6-methoxy-3-(4-nitro-benzyl)-biphenyl (I-34) as a yellow solid. MS (APCI−): 370.1 (M−1).

Provenance & Evidence