Sodium Hydroxide → N-4-Boc-N-1-Cbz-2-piperazine carboxylic acid

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Reaction Steps

A solution 0.164 M of 2-piperazinecarboxylic acid dihydrochloride in a 1:1 dioxane-water mixture was made basic (pH 11) with 50% aqueous NaOH. A 0.68 M solution of Boc-ON (1.1 eq) in dioxane was added dropwise at RT to the above mixture and the reaction mixture was stirred at RT overnight. The mixture was extracted with Et2O (×3) and acidified with conc. HCl to pH 2. The aqueous layer was extracted with EtOAc (×3). The aqueous solution was basified to pH 10 with 50% NaOH. A 0.59 M solution N-(benzyloxycarbonyloxy)succinimide (1.1 eq.) in dioxane was added to the mixture at 0° C. The reaction mixture was stirred 3 h at RT. Dioxane was removed under reduced pressure. The basic solution was extracted with Et2O (×2) then acidified to pH 1 with conc. HCl, and extracted with EtOAc (×3). The combined organic layers were dried and evaporated. The residue was used as such in next step.

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