1,2-Dimethoxyethane → Methyl 4-[2-(hydroxymethyl)-1-benzofuran-5-yl]Benzoate

Participants

Reaction Steps

To 4 mL DME under Ar was added (5-bromo-1-benzofuran-2-yl)methanol (Example 3, 250 mg, 1.10 mmol) and Ar was bubbled through the mixture for 2 minutes to remove any dissolved oxygen. To this mixture was then added 37.6 mg (0.033 mmol) tetrakis(triphenylphosphine) palladium(0) and the reaction was stirred for 10 minutes at rt. 4-(Methoxycarbonyl)phenyl boronic acid (218 mg, 1.21 mmol) and 2.64 mL of 1 M Na2CO3 were then added, and the mixture was then heated to 100° C. for 2.5 hours under Ar. At the end of this time, TLC (5% MeOH/CH2Cl2) revealed complete reaction. The mixture was then filtered and the DME removed under reduced pressure. The thick paste was then transferred to a separatory funnel with 80 mL water and 100 mL EtOAc. The EtOAc was separated and the aqueous phase extracted with EtOAc (2×100 mL). The combined organic layers were dried over Na2SO4, filtered, and solvent removed in vacuo to provide a dark brown solid. The solid was dissolved in a minimal amount of MeOH, fused to silica gel, and purified by flash chromatography (2.5% MeOH/CH2Cl2). The desired product (247.7 mg, 80%) was obtained as a white solid. 1H-NMR (acetone-d6, δ: 3.91 (s, 3H), 4.71 (s, 2H), 6.82 (s, 1H), 7.62 (m, 2H), 7.83 (d, 2H), 7.94 (m, 1H), 8.09 (d, 2H); LRMS (GC/MS/EI) 282 [M]+.

Provenance & Evidence