Thiophenol → tert-butyl (2R,5S)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]-5-[(phenylsulfanyl)methyl]morpholine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

Cyanomethylenetributylphosphorane (2 eq) was added to a stirred mixture of (2R,5R)-5-hydroxymethyl-2-{2-[2-((S)-2-methoxycarbonylamino-3,3-diphenyl-propionylamino)-phenyl]-ethyl}-morpholine-4-carboxylic acid tert-butyl ester (1 eq) and thiophenol (1.5 eq) in toluene (0.04 M). The mixture was stirred at 90° C. for 2 h, cooled to room temperature and evaporated to dryness. The residue was purified by automated silica gel flash chromatography system eluted with a gradient 0% to 100% of EtOAc/Hex to afford tert-butyl (2R,5S)-2-[2-(2-{[N-(methoxycarbonyl)-β-phenyl-L-phenylalanyl]amino}phenyl)ethyl]-5-[(phenylsulfanyl)methyl]morpholine-4-carboxylate which was then treated with TFA following the procedure described in step 2 of Example 2 to afford the title compound.

Provenance & Evidence