Lithium Hydroxide → HCID 178437153, compound

Participants

Reaction Conditions

Reaction Steps

A 100 mL round bottom flask with a stir bar was charged with the product of Example 1B (0.5 g, 2.03 mmol) and 16 mL of dichloromethane. The reaction solution was cooled to 0° C. and AlCl3 (0.811 g, 6.09 mmol) was added in portions. The mixture was allowed to stir for 20 min, and then butyryl chloride (251 μL, 2.44 mmol) was added dropwise. After stirring for 15 minutes, the reaction mixture was slowly pored into a beaker with ice water and diluted with 120 mL of ethyl acetate. The layers were separated and the organic layer washed with 1 N NaHCO3 (×2), brine (×2), dried over Na2SO4, and filtered. Evaporation of the solvents afforded a clear oil. This material was then dissolved in N,N-dimethylfomamide (2 mL) and 140 μL of dimethyl formamide dimethyl acetal was added. The reaction solution was then heated to 95° C., and stirred at this temperature for 10 hours. After this time the reaction solution was cooled to room temperature and the solvents evaporated. The residue was dissolved in 5 mL of ethanol and methyl hydrazine (108 μL, 2.03 mmol) was added. The solution was heated to reflux for 6 hours. Evaporation of the solvents and dissolution in 4:1 tetrahydrofuran/H2O was followed by the addition of lithium hydroxide (100 mg, 2.38 mmol). The reaction mixture was shaken at room temperature for 110 hours (TLC indicated completion of hydrolysis), and then filtered. The solvents were evaporated and the residue taken up in 1:1 DMSO/methanol and purified over RP-HPLC to afford the title product. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06-1.12 (m, 1 H), 1.12-1.18 (m, 3 H), 1.37-1.55 (m, 2 H), 1.55-1.68 (m, 1 H), 1.69-1.78 (m, 1 H), 1.78-1.88 (m, 4 H), 2.09-2.19 (m, 2 H), 2.41-2.48 (m, 1 H), 2.53-2.62 (m, 2 H), 3.76-3.84 (m, 3 H), 7.20-7.28 (m, 2 H), 7.45-7.55 (m, 3 H); MS (ESI) m/z 327 [M+H]+.

Provenance & Evidence