![]() Screening multiple catalysts is often necessary to identify optimal conditions for the reaction. A 10% Pd/C with eggshell deposition is the catalyst of choice for this deprotection. Several different Pd/C variants are commercially available and their relative performances differ quite dramatically depending on the nature of the starting material and the reaction conditions. Dedicated apparatus, such as a Parr shaker hydrogenator would certainly help, while only in certain specific situations, a dedicated autoclave is necessary.Ī key element for the success of the deprotection is the choice of the right catalyst. As there is no need for high hydrogen pressure, standard laboratory glassware can be used. The reaction can be performed in numerous solvents under 1-3 bar H 2 and moderate heat. The Bn protecting group is selectively cleaved by Pd-catalysed hydrogenolysis. The starting material is dissolved in an organic solvent, such as dichloromethane, together with the reagent (the TMSI is usually added dropwise) and the reaction is run under stirring at room temperature for 12-24h. The two reagents that can be used are trimethylsilyl iodide (TMSI) and zinc bromide. The trade off is a slightly more complex reaction set up and longer reaction times, up to 48-72h. They can be useful for acid-labile compounds. Two other common deprotection methods avoid the use of a strong acid. Biphasic systems can be used, with the protected amine dissolved in the organic phase mixed with the aqueous solution of the acid. The reaction is usually fast and happens at room temperature. Concentrated hydrochloric acid, or trifluoroacetic acid (TFA) are the acids of choice. The starting material is dissolved in water or organic solvent, such as toluene, dichloromethane, or ethyl acetate. The deprotection of a BOC-protected amine is a simple carbamate hydrolysis in acidic conditions. Even though this is not strictly an amine protection, the method can be useful in the design of the synthetic strategy. 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.Ĭommon bases for the transformation are sodium hydroxide, 4-dimethylaminopyridine (DMAP) and sodium bicarbonate.Ī completely different route for the preparation of protected amines is the direct reaction of an alkyl halide with di-tert-butyl-iminodicarboxylate. It is typically performed in water, water/THF, THF, or acetonitrile at room temperature or moderate heat (40☌) in the presence of a base. The process usually achieves high yields and fast conversions under relatively mild conditions. The reaction conditions for the amine protection are quite flexible. The BOC (tert-butyloxycarbonyl) protecting group, chemically a di-tert-butyl dicarbonate (Boc 2O), is probably the most common amine protecting group in non-peptide chemistry.
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