Propionic Acid → 5(S)-[1(S)-(Boc-Amino)-2-[p-(2-methoxyethoxy)phenyl]ethyl]-3(R)-[(p-benzyloxyphenyl)methyl]dihydrofuran-2-(3H)-one

Participants

Reaction Conditions

Reaction Steps

Under an N2 atmosphere, 3.6 g (9.48 mmol) of 5(S)-[1(S)-(Boc-amino)-2-[p-(2-methoxyethoxy)phenyl]ethyl]dihydrofuran-2-(3H)-one, dissolved in 17.3 ml of THF and 1.9 ml of DMPU, are deprotonated, at -70° C., with 18.58 ml of a 1 M solution of lithium bis(trimethylsilyl)amide in THF, and, after 15 min, alkylated with 3.07 g (9.48 mmol) of p-benzyloxybenzyl iodide (Example 1d)) in 6 ml of THF. After 30 min at -75° C., the mixture is protonated with 3.53 ml (47.4 mmol) of propionic acid and 3.53 ml of water and warmed to 0° C. The reaction mixture is diluted with 95 ml of ethyl acetate and the whole is washed with 10% citric acid solution, sat. NaHCO3 solution and saline. The aqueous phases are extracted with 2 portions of ethyl acetate. The organic phases are dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 1:1) and crystallization from ethyl acetate/hexane yields the pure title compound: TLC Rf (C)=0.38; tRet (II)=18.0 min; FAB-MS (M+H)+ =576.

Provenance & Evidence