Dimethyl Sulfoxide → HCID 11573447, compound

Temperature

45 °C

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).

1. customA 250 mL round bottom flask equipped with a magnetic stirrer bar and a reflux condenser
2. additionwas added to the clear solution
3. dissolutionuntil most of the solid had dissolved
4. customThe layers were separated
5. washThe organic phase was washed with water (2×50 mL) and brine (1×40 mL)
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated
8. stirringThe orange solution was stirred for 20 hr at 25° C.
9. washwashed with MTBE
10. extractionThe organic phase was extracted with aqueous 3% sodium bicarbonate solution
11. extractionextracted with 60 mL of MTBE
12. washThis organic phase was washed with brine (1×40 mL)
13. dry with materialdried over sodium sulfate
14. concentrationconcentrated
15. customThe residue was purified by flash chromatography

ORD record

ord-66eb14bb044f441c8c3a18ca56fba510

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08273794B2