Dimethyl Sulfoxide → HCID 11573447, compound

Participants

Reaction Conditions

Reaction Steps

A 250 mL round bottom flask equipped with a magnetic stirrer bar and a reflux condenser was charged with 10.32 g (48.2 mmol) of 2,2′-dihydroxybenzophenone and 100 mL of dimethylsulfoxide (DMSO). Potassium hydroxide (2.91 g, 51.9 mmol) that had been ground to a powder was added to the clear solution. The reaction mixture was heated to 45° C., until most of the solid had dissolved. The resulting red slurry was treated with 8.80 mL (11.04 g, 49.5 mmol) of ethyl 6-bromohexanoate. After stirring for 20 hr at 25° C., the clear reaction mixture was diluted with aqueous 1% hydrochloric acid and methyl t-butyl ether (MTBE). The layers were separated. The organic phase was washed with water (2×50 mL) and brine (1×40 mL), dried over sodium sulfate and concentrated. The residue was taken up in 100 mL of tetrahydrofuran (THF) and treated with potassium trimethylsilanoate (15.09 g, 118 mmol). The orange solution was stirred for 20 hr at 25° C., diluted with aqueous 4% hydrochloric acid to pH 7.5 and washed with MTBE. The organic phase was extracted with aqueous 3% sodium bicarbonate solution. The combined aqueous phases were acidified to pH 2 with aqueous 4% hydrochloric acid and extracted with 60 mL of MTBE. This organic phase was washed with brine (1×40 mL), dried over sodium sulfate and concentrated. The residue was purified by flash chromatography using 80% hexanes/ethyl acetate (spiked with 0.5% acetic acid). The product (4.2 g, 27%) was isolated as an off-white solid, mp 89-91° C. Combustion analysis: Found: C, 69.50; H, 6.04%; C19H20O5 requires C, 69.50; H, 6.14% 1H NMR (d6-DMSO): δ 12.0, bs, 1H (COOH); δ 11.5, bs, 1H (OH); δ 7.5, t, 2H, (aryl H's); δ 7.4, dd, 1H (aryl H); δ 7.3, dd, 1H (aryl H); δ 7.15, d, 1H (aryl H); δ 7.1, t, 1H (aryl H); δ 7.0, d, 1H (aryl H); δ 6.9, t, 1H (aryl H); δ 3.9, t, 2H, (CH2 α to O); δ 2.05, t, 2H(CH2 α to COOH); δ 1.4, m, 4H (other two CH2's); δ 1.0, p, 2H(CH2 in middle of chain).

Provenance & Evidence