Hydrochloric Acid → HCID 69055772, compound

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Reaction Steps

(−)-ibuprofen (1.2 g, 5.8 mmol) is dissolved in dioxane (5 mL); thionyl chloride (2.36 mL) is added and the solution obtained is refluxed and left to reflux for 3 hours. After cooling to room temperature, the solvent is evaporated at reduced pressure, and the excess of thionyl chloride is eliminated, dissolving the residue twice with dioxane and evaporating the solvents under high vacuum. An oily yellow residue (1.3 g; 5.79 mmol) is obtained, which is dissolved in dry dichloromethane (2 mL) and added, by means of slow dripping and in an inert atmosphere, to a solution of 2,2-dimethyl-1,3-dioxan-2,5-dione (Meldrum's acid) (0.83 g; 5.79 mmol) and pyridine (1.12 mL; 14 mmol) in dry dichloromethane (5 mL) previously cooled to T=+5° C. with a water/ice bath. Once the additions are completed, the mixture is left for one hour at this temperature and then for another hour at room temperature. The mixture, diluted with dichloromethane is repartitioned with a 2N solution of HCl and crushed ice, under vigorous stirring for approximately 30 min. After separation of the phases, the organic phase, washed with 2N HCl (2×10 mL) and with a saturated solution of NaCl, is dried on Na2SO4 after evaporation of the solvent at reduced pressure, the residue of (R) (+)-5-[2-(4-isobutyl-phenyl)-propion-1-yl]-2,2-dimethyl-1,3-dioxan-4,6-dione ([α]D=+62°; c=1.1% CH2Cl2) without further purifications, is dissolved in methanol (14 mL); the solution is reheated to reflux for 3 hours. After cooling and evaporation of the solvent, the residue is purified by means of flash chromatography (eluent: n-hexane/ethyl ether 8:2) to yield pure methyl ester of (R) (−)-4-[(4′-isobutyl)phenyl]-3-oxopentanoic acid as a colourless oil (0.6 g; 2.28 mmol); [α]D=−192.5° (c=1; CH3OH); 1H-NMR (CDCl3): σ 7.1 (s, 4H); 3.88 (q, 1H, J=8 Hz); 3.67 (s, 3H); 3.47-3.28 (q, 2H, J=8 Hz); 2.45 (d, 2H, J=8 Hz); 1.85 (m, 1H); 1.40 (d, 3H, J=8 Hz); 0.95 (d, 6H, J=7 Hz).

Provenance & Evidence