Amine Protection / Deprotection

11 Nov.,2022



The BOC (tert-butyloxycarbonyl) protecting group, chemically a di-tert-butyl dicarbonate (Boc2O), is probably the most common amine protecting group in non-peptide chemistry. The reaction conditions for the amine protection are quite flexible. The process usually achieves high yields and fast conversions under relatively mild conditions.

It is typically performed in water, water/THF, THF, or acetonitrile at room temperature or moderate heat (40°C) in the presence of a base. Dioxane and methanol have also been reported as solvents for the reaction, while an alternative common method is refluxing a biphasic mixture of chloroform and water, with sodium bicarbonate as a base.

Common bases for the transformation are sodium hydroxide, 4-dimethylaminopyridine (DMAP) and sodium bicarbonate.

A completely different route for the preparation of protected amines is the direct reaction of an alkyl halide with di-tert-butyl-iminodicarboxylate. Even though this is not strictly an amine protection, the method can be useful in the design of the synthetic strategy.