Triethylamine → HCID 22280146, compound

Participants

Reaction Conditions

Reaction Steps

Preparation of [5-Methoxy-2-methyl-4-(2′,4′,6′-trimethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid methyl ester (compound 5A) 2-Bromo-1,3,5-trimethyl-benzene (396 mg, 2mmol), 4-hydroxymethylphenylboronic acid (334 mg, 2.2 mmol), cesium carbonate (1.3 g, 4 mmol), and PdCl2(dppf) (82 mg, 0.1 mmol) were added to 5 ml of a 1:1 solution of DMF/THF. The reaction was flushed with nitrogen and heated to 90° C. for 1 h. The reaction was cooled, poured into diethyl ether and washed with water (2×10 ml), brine (1×10 ml) and dried over anhydrous sodium sulfate. The organic solution was filtered through silica gel, eluted with diethyl ether, and concentrated. The crude product was dissolved in 10 ml dichloromethane. Added to this solution were triethylamine (202 mg, 2 mmol) then methanesulfonyl chloride (184 mg, 1.6 mmol) and allowed to stir at ambient temperature for 18 h. The reaction was poured into water and extracted with methylene chloride. The organic solution was dried over anhydrous sodium sulfate, decanted and concentrated to provide the crude alkyl chloride. The product from Example 1D (387 mg, 1.6 mmol), the crude 4′-chloromethyl-2,4,6-trimethyl-biphenyl, and cesium carbonate (1 g, 3.06 mmol) were stirred in 10 ml acetonitrile for 3 h, filtered, concentrated, and purified by normal phase chromatography to afford the title product. MS m/z 451 (M+1). Step 2. Preparation of [5-Methoxy-2-methyl-4-(2′,4′,6′-trimethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid The title compound was prepared in the manner analogous to Example 1 using 5A. mp 141° C.; 400 MHz 1H NMR (DMSO-d6) δ 12.81 (br(s), 1H), 7.04 (d, 2H, J=8.4 Hz), 6.77 (m, 3H), 6.69 (s, 2H), 6.36 (s, 1H), 4.43 (s, 2H), 3.82 (s, 2H), 3.58 (s, 3H), 2.03 (s, 3H), 1.82 (s, 3H), 1.67 (s, 6H). MS m/z 437 (M+1).

Provenance & Evidence