4-(Hydroxymethyl)benzeneboronic acid → 3-(2-Fluoro-4'-hydroxymethyl-biphenyl-4-yl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one

Participants

Reaction Steps

A degassed mixture containing 3-(3-fluoro-4-iodo-phenyl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one (1.0 g, 2.48 mmol), 4-(hydroxymethyl)phenylboronic acid (0.46 g, 3.00 mmol) and Pd(PPh3)4 in toluene (24 mL), EtOH (8 mL) and H2O (8 mL) was heated to reflux for 15 h. The reaction was concentrated, the crude residue was suspended in H2O, filtered and dried in vacuo to give 3-(2-fluoro-4′-hydroxymethyl-biphenyl-4-yl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one. This crude material was dissolved in CH2Cl2 (10 mL) and Hunig's base (0.88 mL, 5.3 mmol), then MsCl (0.32 mL, 2.65 mmol) was added and the mixture was stirred at room temperature for 15 h. The reaction was partitioned between dilute sodium bicarbonate (NaHCO3, 20 mL) and CH2Cl2 (30 mL). The two layers were separated and the organic phase was washed with saturated ammonium chloride (NH4Cl, 1×20 mL) and H2O (1×20 mL) and dried over Na2SO4. The solvent was evaporated and the crude was purified on silica gel eluting with 0–3% MeOH in CH2Cl2 to give benzyl chloride 107 as white crystalline solid (0.46 g; 43% yield over the last two steps). LCMS (ESI) m/z 403 (M+H)+.

Provenance & Evidence