Cesium carbonate → (2S,5S)-1-tert-butyl 2-(3-(2-((2S,5S)-1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carbonyloxy)acetyl)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (2S,5S)-2-(9-bromo-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl 1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carboxylate (5.95 g, 8.88 mmol) in THF (60 mL) was added (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (3.05 g, 13.3 mmol) and Cs2CO3 (2.31 g, 7.09 mmol). The resulting solution was heated to 50° C. for 18 h. The solution was cooled to room temperature and diluted with EtOAc and washed with aqueous HCl (0.5 M). The aqueous layer was backextracted with EtOAc (2×), and the combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by column chromatography (SiO2, 25-100% EtOAc (5% MeOH)/Hexanes) to provide (2S,5S)-1-tert-butyl 2-(3-(2-((2S,5S)-1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)-5-methylpyrrolidine-2-carbonyloxy)acetyl)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylate (3.116, 43% over 2 steps) as a orange foam. LCMS-ESI+: calc'd for C44H55N3O12: 817.38 (M+). Found: 817.65 (M+).

Provenance & Evidence