Propionic Acid → 5(S)-[1(S)-(Boc-Amino)-2-cyclohexylethyl]-3(R)-[(p-methoxyphenyl)methyl]dihydrofuran-2-(3H)-one

Participants

Reaction Conditions

Reaction Steps

880 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF are added dropwise, at -70° C., under an argon atmosphere and within the space of 20 min, to 130 g (400 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-(3H)-one which is dissolved in 1000 ml of abs. THF and 108 ml of DMPU. After 20 min, a solution of 110 g (443 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 60 ml of abs. THF is added dropwise, and this mixture is thoroughly stirred at -75° C. for 2 h. The mixture is subsequently protonate at -70° C. with 152 ml of propionic acid followed by 250 ml of water (temperature rises to -20° C.); 1 l of ethyl acetate is then added and the reaction mixture is poured onto 2 l of 15% NaHCO3 solution. The aqueous phase is separated off and extracted with 1 l of ethyl acetate. The organic phases are washed 2× with sat. NaHCO3 solution, water and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane yields the pure title compound: TLC Rf (E)=0.45; tRet (II)=18.6 min; FAB-MS (M+H)+ =432.

Provenance & Evidence