Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Babcock_Hall on August 11, 2022, 07:56:42 AM
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We often work with N-Boc protected compounds, and the extraction protocols sometimes call for 1 M HCl. Even if the next step were washing with bicarbonate, this makes me uneasy, due to possible loss of the N-Boc group. However, I am uncertain of the best alternative and whether or not the best alternative depends on context. Using 0.1 M HCl or using 5% NaHSO4 or KHSO4 are possible alternatives. I occasionally see citric acid in wash steps, and I imagine its chelating abilities might be useful in certain work-ups. This question has come up before, but I don't recall that it was resolved.
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Even just 5% HOAc might be sufficient, this type of things can be tested in small scale in a test tube with a pasteaur pipette. what are you washing out?
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I used 5% HCl (95/5 water conc. HCl) or 10% citric acid and no issues so far
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Great! 1M HCl is probably old procedure.
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Wernic D. and collaborators (J. Org. Chem. 1989 54:4224) synthesized 1-tert-Butyl L-2-(t-Boc-amino)-4-oxobutanoate from the corresponding Weinreb amide using 1.5 equivalents of DIBAL-H. “The reaction mixture was partitioned between 0.35 M NaHSO4 aqueous solution (200 mL) and ether (300 mL) and the aqueous layer was extracted with ether (3 X 100 mL). The combined ethereal solutions were washed with 1 M HCl (3 X 100 mL), 1 M NaHCO3 (3 X 100 mL), and brine (3 X 100 mL) and dried (Na2SO4).”
Zhang G. and collaborators (Org Biomol Chem 2015 13(14):4149; Supplemental DOI: 10.1039/c5ob00120j) performed an almost identical synthesis. “The reaction mixture was partitioned between 0.35 M NaHSO4 aqueous solution (20 mL) and ether (30 mL) and the aqueous layer was extracted with ether (3 X 10 mL). The combined ethereal solutions were washed with 1 M HCl (3 X 10 mL), 1M NaHCO3 (3 X 10 mL) and brine (3 X 10 mL) and dried with anhydrous Na2SO4.
Both of these examples quench the reduction with NaHSO4 prior to extraction. Both use 1 M hydrochloric acid. I will look for other chemistry and post when I find it.