83% |
With di-tert-butyl peroxide; dichloro[4,5-bis(diphenylphosphino)-9,9’-dimethylxanthene]palladium(II) at 120℃; for 16h; |
39 Synthesis of Ibuprofen
p-Isobutyl ethylbenzene (2.4 g), ethanol (46 mg), TBP (73 mg, 1 equivalent), and Pd(Xantphos)Cl2 (3.8 mg, 1 mol %) were added into a reaction kettle, into which 10 atm carbon monoxide was introduced. The reaction was heated to 120° C., and stirred at this constant temperature for 16 h. After the reaction was completed, carbon monoxide was discharged, and 97 mg carbonylated ester product was obtained by column chromatography, in a yield of 83%. 1HNMR (400 MHz, CDCl3) δ 0.91 (d, J=6.4 Hz, 6H), 1.29 (t, J=7.2 Hz, 3H), 1.61 (d, J=6.4 Hz, 3H), 1.82-1.84 (m, 1H), 2.43 (d, J=6.4 Hz, 2H), 3.78 (d, J=6.8 Hz, 2H), 4.21 (q, J=7.2 Hz, 2H), 7.05 (d, J=6.8 Hz, 2H), 7.24 (d, J=6.8 Hz, 2H); 13CNMR (100 MHz, CDCl3) δ 13.7, 14.1, 22.8, 29.0, 40.2, 40.4, 44.5, 61.6, 128.8, 128.9, 132.2, 140.2, 173.7; HRMS (ESI) calcd. for C15H22NaO2 [M+Na]: 257.1517. found: 257.1514. The ester product obtained was dissolved in 1,4-dioxane. 6 N sodium hydroxide solution was added, and the reaction was heated to 60° C. After 2 h of reaction, the pH value was adjusted to 1 by adding 2 N hydrochloric acid. After removing the organic solvent under reduced pressure, 83 mg product ibuprofen was obtained by extraction with ethyl acetate, and the yield of hydrolysis was 97%. |