3-Hydroxyisovaleric acid → HCID 66733825, compound

Participants

Reaction Steps

3-hydroxy-3-methyl butyric acid (1.20 equiv), DIPEA (2.00 equiv), and T3P (1.50 equiv) were added to a stirring solution of compound 1 (1.00 equiv) in THF (0.2M) at room temperature under nitrogen. TLC analysis after 2 hours showed almost complete conversion, so reaction was concentrated. Residue was dissolved in ethyl acetate then washed with water, dilute HCl, saturated NaHCO3, and brine. The phases were separated and the organics dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by flash column chromatography (SiO2, 12 g; 0% to 10% methanol in methylene chloride). The resulting material was dissolved in methylene chloride (0.97M) and TFA (0.97M) was added under nitrogen and the mixture was stirred at room temperature for 1 hour at which time HPLC analysis indicated the reaction was complete. Reaction was concentrated and the resulting residue was dissolved in 1N NaOH and stirred at room temperature for 30 minutes. The aqueous mixture was extracted with methylene chloride. The phases were separated and the organics dried over sodium sulfate, filtered, and concentrated affording the title compound, 1-(4-aminopiperidin-1-yl)-3-hydroxy-3-methylbutan-1-one. 1H NMR (300 MHz, CDCl3) δ 4.40 (d, 1H, JHz=13.9), 3.73 (d, 1H, JHz=12.1), 2.99-2.95 (m, 1H), 2.90 (m, 1H), 2.70-2.63 (m, 1H), 2.33 (s, 2H), 1.76 (m, 2H), 1.12 (s, 8H).

Provenance & Evidence