Ammonium Hydroxide → (S)-2-Amino-5-benzyloxycarbonylamino-pentanoic acid methyl ester

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Reaction Steps

Alkylated Troc-Orn(Z)—OMe (xlv). To a biphasic mixture of EtOAc (20 mL) and sat. NH4OH (20 mL) was added solid H-Orn(Z)—OMe.HCl (184 mg, 0.582 mmol). The mixture was shaken in a separatory funnel until the solid dissolved. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure to afford the free amine of H-Orn(Z)—OMe. To a solution of this amine (142 mg, 0.507 mmol) in anhydrous CH2Cl2 (5 mL) were added 4 Å molecular sieves. To this suspension was added a solution of aldehyde xliii (84 mg, 0.49 mmol) in CH2Cl2 (2 mL). After stirring at it for 20 h, solid NaCNBH3 (48 mg, 0.76 mmol) was added in two portions 45 min apart. The reaction was stirred for 18 h, and the mixture was then filtered. The filtrate was concentrated under reduced pressure, redissolved in EtOAc, poured over sat. Na2CO3 (aq), and washed with 5% citric acid (aq). The organic layer was then separated, dried over MgSO4, filtered and concentrated under reduced pressure to afford a crude oil that was used without further purification. To a solution of the crude secondary amine in anhydrous THF (5 mL) were sequentially added triethylamine (0.149 mL, 108 mg, 1.07 mmol) and 2,2,2-trichloroethyl chloroformate (0.101 mL, 155 mg, 0.73 1 mmol). A white precipitate immediately formed, and after stirring for 15 min, the reaction was quenched with sat. NaHCO3 (aq). The resulting mixture was poured over EtOAc, and the organic layer was washed with 5% citric acid (aq), sat. NaHCO3 (aq) and brine. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. Column chromatography afforded the desired product xlv (98 mg, 0.16 mmol, 32% two steps).

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