Deprotection of a Methyl Ester Using LiOH

April 1st, 2007

 

The above methyl ester (2.5 g, 7.6 mmol) was suspended in 140 mL of THF in a 500-mL round-bottomed flask. In a separate flask, 2.5 g of lithium hydroxide was dissolved in 140 mL of deionized water. Both mixtures were chilled to 4 °C and combined to form a turbid white mixture. After 1 h of stirring, the mixture had become homogeneous. After 24 h, 50 mL of 3 M HCl was added, and the mixture was allowed to warm to room temperature. Following the addition of a 100-mL portion of saturated aqueous NaCl solution, the mixture was extracted four times with 100-mL portions of EtOAc, and the combined organic layers were evaporated. Yield 2.28 g (7.25 mmol, 95%). White powder. 1H NMR (400 MHz, DMSO-d6): 11.99 (s, 1H), 8.39 (t, J = 5.9 Hz, 1H), 7.74 (d, J = 8.5 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.28 (s, 2H), 4.29 (d, J = 6.0 Hz, 2H), 2.20 (t, J = 6.9 Hz, 2H), 2.14 (t, J = 7.0 Hz, 2H), 1.49 (m, 4H). 13C NMR (126 MHz, DMSO-d6): 175.09, 172.76, 144.55, 143.22, 128.11, 126.36, 42.32, 35.68, 34.07, 25.47, 24.84. High Resolution ESI-MS: 315.1005. Calculated for C13H19N2O5S+ [M+H+]: 315.1009.

Previous Comments

  1. carbazole Says:
    April 3rd, 2007 at 12:11 am I had a series of alpha-beta unsaturated esters that just refused to be saponified by LiOH in H2O/THF, even after refluxing for days. I switched to KOH in 4:1 MeOH/H2O, and that did the trick. It’s a little less fun to work up, because you have to remove most of the methanol, but if the THF/H2O isn’t working, it’s a good alternative. Good yields (only missed what was left on the flasks).
  2. Hap Says:
    April 3rd, 2007 at 11:25 am I thought LiOH/H2O2 was the next step up for hydrolyses (no for a,b-unsatd. esters) – it’s used to hydrolyse Evans’s amides (I don’t know if it’ll hydrolyze the sulfonamide).
  3. Javaslinger Says:
    July 23rd, 2007 at 9:27 am I was able to use your method perfectly for a borylated ester compound. Worked perfectly in good yield. Thanks!Ken

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