Water → (3R,10S)-5-methyl-3-(9-oxo-1,8-diaza-tricyclo-[10.6.1.013,18]nonadeca-12(19), 13(18), 14,16-tetraen-10-ylcarbamoyl)hexanoic acid t-butyl ester

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Reaction Steps

Alternatively, to a solution of (2R)-4-methyl-2-(t-butoxycarbonylmethyl)pentanoic acid as prepared above (2.39 g, 10.4 mmol), HOBt.H2O (2.5 g, 1 eq.), N-methylmorpholine (2.3 mL, 2 eq.), and (10S)-10-amino-(9-oxo-1,8-diazatricyclo[10.6.1.013,18 ]nonadeca-12(19),13(18),14,16-tetraene (2.96 g, 1 eq.) in dry DMF (200 mL) under argon was added EDCI (3.96 g, 2.0 eq.). The resulting mixture was stirred overnight, then the next morning the DMF was removed at 35° C. under high vacuum. The residue was partitioned between CH2 Cl2 (150 mL)/water (75 mL), then the organic layer was washed with 0.5N HCl (2×75 mL), saturated NaHCO3 (2×75 mL) and finally with brine (1×75 mL). After drying the CH2Cl2 layer over Na2SO4, it was filtered and evaporated to dryness. Purification by column chromatography (petroleum ether to 30% ethyl acetate/petroleum ether) gave (3R,10S)-5-methyl-3-(9-oxo-1,8-diaza-tricyclo[10.6.1.013,18 ]nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanoic acid t-butyl ester (3.24 g, 62.7%).

Provenance & Evidence