1-Fluoro-2-nitrobenzene → (2S,3S)-2-tert-butoxycarbonylamino-3-(2-nitro-phenylamino)-butyric acid methyl ester

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Reaction Steps

A suspension (2S,3S)-3-amino-2-tert-butoxycarbonylamino-butyric acid methyl ester (6.0 g, 20.7 mmol) (prepared according to WO 2010031750), 1-fluoro-2-nitrobenzene (4.37 g, 31.0 mmol) and sodium hydrogen carbonate (5.21 g, 62 mmol) in N,N-dimethylformamide (60 ml) was heated to 85° C. for 24 h. The reaction was cooled, concentrated in vacuo and the residue was diluted with water (100 ml) and extracted with ethyl acetate (2×150 ml). The organic layers were combined, washed with water (1×50 mL), brine (1×50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 5 to 60% v/v ethyl acetate hexanes to give (2S,3S)-2-tert-butoxycarbonylamino-3-(2-nitro-phenylamino)-butyric acid methyl ester (5.71 g, 78%).

Provenance & Evidence