tert-butyl (2S)-2-amino-4-methylpentanoate → tert-Butyl (S)-2-((S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetate

Participants

Reaction Steps

4.8 g of L-leucine tert-butyl ester isocyanate (prepared from L-leucine tert-butyl ester analogously to J. S. Nowick et al., J. Org. Chem. 1996, 61, 3929) were added to a solution of 5.8 g (22.5 mmol) of 169.1 in 50 ml of DMF. After stirring at room temperature for 4 h, the solvent was removed and the residue was chromatographed on silica gel using heptane/tert-butyl methyl ether=6/4. The fractions containing the intermediate were combined, the solvent was removed in vacuo, the residue was dissolved again in 90 ml of absolute DMF and the solution was treated at 0° C. with 775 mg of a 55-65% strength sodium hydride dispersion in oil. After stirring at room temperature for 3 h, the solvent was removed in vacuo and the residue was chromatographed on silica gel using heptane/tert-butyl methyl ether=1/1. After concentration of the product fractions, 7.8 g (79%) of 169.2 were obtained as a colorless solid.

Provenance & Evidence