Nω-CBz-L-Ornithine
Potassium hydroxide
Trimethylacetyl chloride
Hydrogen
palladium hydroxide (20% on carbon)

Nω-CBz-L-Ornithine (31.92 g, 120 mmol) was added to a mixture of KOH (6.72 g, 120 mmol), water (200 ml) and THF (100 ml) at 0 ºC. Trimethylacetyl chloride (12.3 ml, 100 mmol) was added dropwise keeping the internal temperature below 10 ºC. The reaction was stirred for 14 hours. The mixture was then extracted with 1:1 EtOAc / 40-60 petroleum ether (2 × 200 ml). Aqueous HCl (6 M) was then added until the solution was pH 2. The mixture was then extracted with ethyl acetate (4 × 200 ml), and the combined extracts were dried over Na₂SO₄ and then reduced in vacuo to give a thick colourless oil. This oil was dissolved in MeOH (650 ml), palladium hydroxide (20% on carbon, 400 mg) was added, and the mixture was stirred at ambient temperature under hydrogen (1 atm.) for 14 hours. The mixture was then filtered through a pad of celite and the solvent was removed in vacuo to give the target compound as a white solid (14.9 g, 69%).

The lower price, or increases ease of synthesis, of Nω-Cbz-ornithine and lysine compared to Nω-Boc-ornithine and lysine can make them preferable starting materials for the synthesis of ornithine or lysine Nα-mono-amides. The decreased water solubilities of Cbz-amide intermediates compared to Boc-amide intermediates also result in increase yields for the first step. Importantly however the un-acylated Cbz ornithine or lysine is water soluble enough at low pH to be extracted into aqueous acid (or pH 2 aqueous sulfate buffer, 0.5 M Na₂SO₄ / 0.5 M NaHSO₄). This extraction allows the use of excess protected amino-acid starting material. In turn this ensures complete reaction of the acid chloride and clean pre-hydrogenolysis intermediate. The Cbz removal by hydrogenolysis is simple to perform, and after filtration and reduction in vacuo results in analytically clean product as a neutral molecule. Acid-mediated Boc removal usually results in the formation of a ammonium salt product which has be subjected to another procedure (e.g. ion exchange chromatography) to generate the overall-neutral product. The ability to generate very clean material, at the expense of a slight reduction is yield, can be very important, especially if the reaction is being performed on large scale where chromatography is not practical or crystallisation not possible.

δ_H(400MHz, D₂O) 4.14 (1H, dd J 7, 5, CHN), 2.93 (2H, t, J 7 CH₂N), 1.87-1.76 (1H, m, CH₂), 1.73-1.54 (3H, m, CH₂), 1.13 (9H, s, (CH₃)₃) (NH and OH missing).