Lithium Hydroxide → HCID 10119718, Verbindung

A mixture of Example 5C (55 mg, 0.20 mmol) and 1M LiOH (0.3 mL) in THF (2 mL) was heated to 50° C., stirred for 3 hours, concentrated, dissolved in DMF (0.5 mL), and treated with a mixture of Example 3A (60 mg, 0.20 mmol), EDCI (96 mg, 0.50 mmol), and DMAP (10 mg) in dioxane (2.0 mL). The mixture was stirred for 16 hours, diluted with ethyl acetate (50 mL), washed sequentially with 1M HCl (5 mL), water (5 mL), and brine (5 mL), dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel, with 50% ethyl acetate/hexanes to provide a ˜2:1 mixture of diastereomers. MS (ESI(−)) m/e 540 (M−H)−; 1H NMR (400 MHz, DMSO-d6) δ 8.63 (2d, 1H total), 8.33 (2d, 1H total), 7.95 (m, 1H), 7.82 and 7.78 (2d, 2H total), 7.45 (m, 1H), 7.30 (m, 2H), 3.71 (m, 1H), 2.28-0.95 (m, 20H), 0.86 and 0.75 (2s, 9H total).

1. concentrationconcentrated
2. dissolutiondissolved in DMF (0.5 mL)
3. stirringThe mixture was stirred for 16 hours
4. washwashed sequentially with 1M HCl (5 mL), water (5 mL), and brine (5 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe concentrate was purified by flash column chromatography on silica gel, with 50% ethyl acetate/hexanes
9. customto provide
10. additiona ˜2:1 mixture of diastereomers

ORD-Eintrag

ord-fac8088bf15d4b7f94206eb9b80469cc

Quelldatensatz

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07754886B2