Citric Acid → 5(S)-[1(S)-(Boc-Amino)-2-phenylethyl]-3(R)-[(2,4-dimethoxyphenyl)methyl]-dihydrofuran-2-(3H)-one

Participants

Reaction Steps

A solution of 3.57 g (11.7 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]dihydrofuran-2-(3H)-one [Example 2b)] in 12 ml of abs. THF and 2.35 ml of DMPU (1.65 equivalents) is cooled down to -75° C., under argon, and is treated dropwise, at an internal temperature of less than -70° C. and over a period of 30 min, with 22.9 ml (1.96 equivalents) of a 1M solution of lithium bis(trimethylsilyl)amide in THF (Aldrich, Steinheim, FRG). After a further 15 min, 25 ml of a toluene solution containing approximately 1 equivalent of 2,4-dimethoxybenzyl bromide is added dropwise to this mixture, over the space of 20 min, and this mixture is allowed to react at -70° C. for 2 h. 4.36 ml of propionic acid and 4.36 ml of water are then added to this solution and the temperature is allowed to rise to 0° C. The reaction mixture is diluted with 200 ml of (cold) ethyl acetate and stirred up for 5 min with 60 ml of (cold) 10% citric acid. After that, the phases are separated. The organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and with saline once again, dried over Na2SO4 and concentrated. The title compound is isolated by flash chromatography on silica gel (E). TLC Rf (E)=0.24.-FAB-MS (M+H)+ =455.-HPLC tRet =16.85 min (gradient II). IR(CH2 Cl2)=inter alia 3429, 1769, 1712, 1613 and 1506 cm-1.-1 H-NMR(CDCl3)=inter alia 7.34-7.10/m (5H); 6.98/d (1H); 6.45-6.291m (2H); 4.31/txd (1H); 3.78 and 3.71/each s (each 3H); 3.08 and 2.66/each d×d (each 1H); 1.35/s (9H).

Provenance & Evidence