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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: scattolintmirati.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 75C 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