A Nucleophilic Deprotection of Carbamate Mediated by 2-Mercaptoethanol
Thomas Scattolin*, Tawfik Gharbaoui and Cheng-yi Chen
*Mirati Therapeutics, 3545 Cray Court, San Diego, California 92121, United States,
Email: scattolint
mirati.com
T. Scattolin, T. Gharbaoui, C.-y. Chen, Org. Lett., 2022, 24, 3736-3740.
DOI: 10.1021/acs.orglett.2c01410
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Abstract
Cbz, Alloc, and methyl carbamate protected amines can be readily deprotected by treatment with 2-mercaptoethanol in the presence of potassium phosphate in N,N-dimethylacetamide at 75 °C. This nucleophilic deprotection protocol is superior to the standard hydrogenolysis or Lewis acid-mediated deprotection conditions for substrates bearing sensitive functionalities.
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proposed mechanism
experimental and computational study of various carbamates
General Procedure for the Deprotection of Carbamate Protecting Group
A suspension of protected amine (1 equiv.) with potassium phosphate tribasic (4 equiv.) in DMAc (0.25 M) was purged 3 times with N2. Then 2-mercaptoethanol (2 equiv.) was added and reaction was stirred at 75°C for 24 h. The mixture was cooled to room temperature then poured into water, the aqueous phase was extracted with DCM and then back extracted with DCM (1-2 x). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a crude product. The residue was purified by column chromatography (SiO2) or reverse phase HPLC to afford the corresponding unprotected amine.
Key Words
Cbz-protected amines, Cleavage of carbamates
ID: J54-Y2022
