Lithium Hydroxide → (6S,9R)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-6,9-diol

Participants

Reaction Steps

In a 250 mL round-bottom flask was dissolved (6S,9R)-6-(2,3-difluorophenyl)-6-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-nitrobenzoate (125 mg, 0.284 mmol) in tetrahydrofuran (2 mL) to give a colorless solution. Lithium hydroxide (0.568 mmol) was added, and the mixture was stirred at room temperature for 2 h. LCMS indicated complete conversion. It was diluted with ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried, and concentrated to a white solid. Purification by FCC up to 6% methanol/methylene chloride afforded the desired product as a white crystalline solid (71 mg, 86%). A few crystals were picked out and an x-ray structure was obtained to confirm the cis-diol stereochemistry. MS(ESI)[M+H+]=292.21; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.44 (d, J=4.58 Hz, 1H) 7.38-7.51 (m, 2H) 7.19 (dd, J=7.48, 5.04 Hz, 1H) 7.04-7.16 (m, 2H) 5.99 (br. s., 1H) 4.90 (dd, J=11.29, 2.14 Hz, 1H) 3.80-3.91 (m, 1H) 2.92 (dd, J=14.65, 2.14 Hz, 1H) 2.57-2.70 (m, 1H) 2.37 (br. s., 1H) 2.11 (ddd, J=14.19, 5.95, 3.97 Hz, 1H) 1.96-2.06 (m, 1H) 1.74-1.91 (m, 1H); 19F NMR (470 MHz, CHLOROFORM-d) δ ppm −138.91-−138.74 (m, 1F) −139.22-−139.06 (m, 1F); 13C NMR (126 MHz, CHLOROFORM-d) δ ppm 160.64 (s, 1C) 152.00-150.10 (dd, J=21.42 and 254.52 Hz, 1C) 148.75-146.71 (dd, J=11.52 and 244.44 Hz, 1C) 145.55 (s, 3C) 139.91 (s, 3C) 138.44 (d, J=8.64 Hz, 1C) 129.37 (s, 1C) 123.89-124.57 (m, 2C) 122.48 (s, 3C) 120.84 (s, 1C) 116.22 (d, J=17.28 Hz, 2C) 71.79 (m, 3C) 71.70 (m, 4C) 44.30 (d, J=4.80 Hz, 2C) 39.65 (s, 1C) 31.29 (s, 2C).

Provenance & Evidence