Citric Acid → 5(S)-[1(S)-(Boc-amino)-2-(p-benzyloxyphenyl)-ethyl]-3(R)-(p-benzyloxyphenylmethyl)-dihydrofuran-2-(3H)-one

Participants

Reaction Conditions

Reaction Steps

2.47 g (6.0 mmol) of 5(S)-[1(S)-(Boc-amino)-2-(p-benzyloxyphenyl)ethyl]dihydrofuran-2-(3H)-one dissolved in 12 ml of THF and 1.2 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone are treated, at -70° C. and under a protective gas, with 11.73 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF, and this mixture is stirred for 15 min; it is then alkylated with 1.946 g (6.0 mmol) of p-benzyloxybenzyl iodide (Example 1d)) in 3 ml of THF (60 min). For hydrolysing, 2.23 ml of propionic acid and 2.23 ml of water are added and the mixture is warmed to 0° C. The reaction mixture is poured onto 30 ml of 10% citric acid solution, and this mixture is extracted twice with ethyl acetate; the organic phases are washed twice with saturated NaHCO3 solution and, finally, with saline. Drying the organic phases with Na2SO4 and evaporating them, and column chromatography (SiO2, hexane/ethyl acetate 4:1) of the residue, and subsequent crystallization from ethyl acetate/hexane, affords the pure title compound: TLC Rf (D)=0.45; tRet (I)=19.9 min; FAB-MS (M+H)+ =608.

Provenance & Evidence