Citric Acid → Phenylmethyl N-[(5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-6-oxohexyl]carbamate

Participants

Reaction Steps

To a solution of 0.975 g of Boc-Lys(Cbz)-OMe in 25 ml of dichloromethane at −78° C. under a nitrogen atmosphere was added 6 ml of a 1M diisobutylaluminiumhydride solution in hexane. After 15 min the reaction was completed, the reaction mixture poured into 150 ml of 2% citric acid solution and filtered. The organic layer was separated, washed with water and brine, dried (magnesium sulfate) and concentrated. The residue was coevaporated with toluene to give 0.92 g of Boc-Lys(Cbz)-H. This aldehyde (0.89 g) was dissolved in 1.4 ml of toluene and 0.90 g of 2-(trimethylsilyl)oxazole (prepared according to: Edwards, P. D., Wolanin, D. J., Andisik D. W., and Davis W., J. Med. Chem. 38, 76 (1995)) was added and heated at 80° C. After 60 h the reaction mixture was concentrated, the residue dissolved in 5 ml of tetrahydrofuran, treated with 3 ml of a 3M tetrabutylammonium fluoride in tetrahydrofuran solution and stirred at room temperature for 2 h. The mixture was concentrated dissolved in ethyl acetate, washed with 3% aqueous sodium hydrogencarbonate solution and brine, dried (magnesium sulfate) and evaporated. Purification by column chromatography on silica gel eluting with a gradient of ethyl acetate/dichloromethane=2/1 (v/v) to ethyl acetate afforded an oil that was rechromatographed on silica gel eluting with a gradient of ethyl acetate/heptane=1/1 (v/v) to ethyl acetate/heptane=1/3 (v/v) to give 0.22 g of the title compound.

Provenance & Evidence