Ammonium Chloride → (3R,4S,5S)-tert-butyl 4-((S)-2-(((benzyloxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate

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Reaction Steps

425 mg (1.7 mmol) of N-[(benzyloxy)carbonyl]-L-valine were dissolved in 50 ml of DMF, and 500 mg (1.7 mmol) of tert-butyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoate hydrochloride (Starting Material 2), 356 mg (1.9 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 285 mg (1.9 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 655 mg (5.1 mmol) of N,N-diisopropylethylamine were added in succession. The mixture was stirred at RT for 20 h. Another 142 mg (0.5 mmol) of N-[(benzyloxy)carbonyl]-L-valine, 119 mg (0.6 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 95 mg (0.6 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 218 mg (1.7 mmol) of N,N-diisopropylethylamine were added, and the mixture was treated with ultrasound for 90 min. The mixture was then poured into a mixture of semisaturated aqueous ammonium chloride solution and ethyl acetate. The organic phase was separated off, washed successively with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. The residue was purified by preparative HPLC. This gave 329 mg (40% of theory) of the title compound as a colourless oil.

Provenance & Evidence