Phosphorus tribromide → HCID 23503539, compound

Participants

Reaction Steps

To a solution of 4-(propyloxy)-3-methoxybenzyl alcohol (2.28 g, 11.62 mmol) in anhydrous diethyl ether (30 mL) was slowly added PBr3 (0.55 mL, 5.81 mmol) via syringe, and the resulting mixture was stirred at room temperature for 2 hours. The mixture was diluted with diethyl ether (150 mL) and washed with saturated aqueous NaHCO3 (2×75 mL) and brine (2×75 mL). The organic layer was dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford 4-(propyloxy)-3-methoxybenzyl bromide (2.94 g, 98%) as a white solid. n-Butyllithium (2.5 M solution in hexanes, 0.56 mL, 1.40 mmol) was added to a solution of diisopropylamine (0.20 mL, 1.42 mmol) in dry THF (4 mL) at −78° C. The mixture was stirred at −78° C. for one hour, then HMPA (0.33 mL, 1.91 mmol) was added, followed by adding a solution of compound 21 (0.30 g, 1.27 mmol) in THF (3 mL). After 1 hour, a solution of 4-(propyloxy)-3-methoxybenzyl bromide (0.658 g, 2.54 mmol) in THF (3 μL) was added in one portion to the reaction, and the resulting mixture was stirred at −78° C. for an additional 4 hours. The excess base was quenched with saturated aqueous NH4Cl (15 mL), and the resulting solution was extracted with EtOAc (3×25 mL). The combined organic layer was washed with saturated NaCl (2×30 mL), dried over MgSO4, filtered and the filtrate evaporated to dryness. The residue was purified by column chromatography on silica gel (hexanes/EtOAc, 2:1) to give compound 137 (0.302 g, 57%) as a white foam.

Provenance & Evidence