Dichloromethane → HCID 53744375, compound

Participants

Reaction Steps

To a stirred solution of 2N K2CO3 (108 mL) was added dioxane (875 mL), 3-bromo-4-(2-hydroxyethoxy)-5-iodobenzoic acid ethyl ester (25.34 g, 61.05 mmol), 4-methoxyphenyl boronic acid (12.43 g, 79.37 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with CH2Cl2 (1.49 g, 1.83 mmol). After stirring at room temperature for 1 h, the mixture was heated at 60° C. for 2.5 h. Progress was monitored by TLC. Additional quantities of catalyst and boronic acid (0.5 g) were added to push the reaction to completion. The reaction was cooled and partitioned between ethyl acetate/0.5 N HCl. The organic phase was washed with 0.5 N HCl, then brine. It was dried (MgSO4), decolorized (charcoal), and concentrated to give a residue which was filtered through a pad of SiO2. Purification by HPLC (ethyl acetate/hexane) afforded 11.47 g (47.5%) of mono-arylated product as a white solid [1H NMR (DMSO-d6) δ 8.08 (d, 1H), 7.82 (d, 1H), 7.50 (d, 2H), 7.02 (d, 2H), 4.65 (t, 1H), 4.30 (q, 2H), 3.81 (s, 3H), 3.59–3.42 (m, 4H), 1.29 (t, 3H)] and 6.61 g (25.6%), of bis-arylated product as a brown oil: 1H NMR (DMSO-d6) δ 7.82 (s, 2H), 7.52 (d, 4H), 7.00 (d, 4H), 4.30 (q, 2H), 3.80 (s, 6H), 3.25 (m, 2H), 3.12 (m, 2H), 1.31 (t, 3H).

Provenance & Evidence