Potassium Carbonate → (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoate

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Reaction Steps

A solution of 2-bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (613) (566 mg, 1.674 mmol) and (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-3-oxohexanoate (614) (995 mg, 2.465 mmol) in DMF (9 mL) was cooled in an ice-water bath and treated with K2CO3 (509 mg, 3.68 mmol) The mixture was stirred for 16 h at RT then heated at 60° C. in an oil bath for 4 h. The mixture was extracted into CHCl3 (3×100 mL) from saturated aq. NaHCO3 (100 mL), dried (Na2SO4), concentrated, and purified by flash chromatography on silica gel (40 g) eluting with a gradient of 0-10% EtOAc in DCM to give (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoate (352a) (247 mg, 0.374 mmol, 22% yield) as a yellow foam. LC-MS m/z 661.1, [M+H]. A solution of (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoate (352a) (247 mg, 0.374 mmol) in EtOH (3.0 mL) and AcOH (1.5 mL) was treated with NH4OAc (Aldrich) (432 mg, 5.61 mmol). The resulting yellow solution was heated at 60° C. for 64 h. The mixture was concentrated and extracted into EtOAc (3×100 mL) from saturated aq. NaHCO3 (150 mL). The organic extracts were dried (Na2SO4), concentrated, and purified by flash chromatography on silica gel (gradient: 0-15% EtOAc in DCM) to give the title compound (352b) as a yellow foam (184.5 mg). LC-MS m/z 642.2, [M+H]+.

Provenance & Evidence