Imidazole → N-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-3-nitro-2-pyridinamine

Participants

Reaction Steps

To a solution of (2R)-2-{[6-(methyloxy)-3-nitro-2-pyridinyl]amino}-3-[(phenylmethyl)oxy]-1-propanol (675.8 g) in DMF (2.37 L) was added chloro(1,1-dimethylethyl)dimethylsilane (382.0 g) in portions. Then, imidazole (331.2 g) was added in portions and the mixture was stirred at room temperature for 1.5 h. The reaction mixture was evaporated and the resulting orange gum was partitioned between EtOAc (3 L) and H2O (3 L). The layers were separated and the aqueous was extracted with EtOAc (2.5+2 L). The organic layers were combined, dried over MgSO4 (˜500 g), filtered and evaporated to give an orange oil. The crude product was purified by column chromatography (10 kg silica, 9:1 heptane:EtOAc) to give N-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-3-nitro-2-pyridinamine (774.7 g, 100%) as a bright yellow solid.

Provenance & Evidence