Lithium Hydroxide → HCID 22730282, Verbindung

A mixture of Example 455B (1 g, 3.1 mmol) and LiOH (0.264 mg 6.2 mmol) in THF (15 mL), methanol (2.5 mL), and water (1.5 mL) was heated to 50° C. for 3 hours and concentrated. The concentrate was dissolved in DMF (10 mL) and treated with a mixture of Example 77B (1.059 g, 3 mmol), EDCI (1.146 g, 6 mmol), and DMAP (1.830, 15 mmol) in dichloroethane (10 mL), stirred for 16 hours, diluted with ethyl acetate (250 mL0, washed sequentially with 1N HCl (50 mL, water (100 mL) and brine (100 mL), dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane to provide the desired product. MS (ESI(−)) m/e 637 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ8.78 (br t, 1H), 8.60 (d, 1H), 7.92 (dd, 1H), 7.85 (d, 2H), 7.55 (d, 2H), 7.40-7.15 (m, 6H), 6.35 (m, 1H), 4.21 (d, 2H), 3.65 (m, 2H), 3.52 (t, 2H), 3.25 (m, 4H), 1.45 (s, 9H).

1. concentrationconcentrated
2. dissolutionThe concentrate was dissolved in DMF (10 mL)
3. washwashed sequentially with 1N HCl (50 mL, water (100 mL) and brine (100 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe concentrate was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane

ORD-Eintrag

ord-ec1bea58b6484f58bc37baff3055fbb5

Quelldatensatz

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06720338B2