反应详情

To a solution of N2-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-2,3-pyridinediamine (673.1 g, 1.612 mol) in DMF (10 L) was added K2CO3 (490.1 g, 3.546 mol). Ethyl bromoacetate (196.6 ml, 1.77 mol) was added to the mixture over 15 min and the reaction mixture was stirred at room temperature. After 3 h, the reaction was quenched in H2O (10 L) then partitioned with EtOAc (10 L). The layers were separated and the aqueous was extracted with EtOAc (7 L). The organic phases were combined, washed with H2O (7 L) and brine (7 L), dried over MgSO4 (1 kg), filtered and evaporated. The resulting dark oil (853 g) was purified by column chromatography (9 kg silica, mixtures of heptane and EtOAc as eluent) to give ethyl N-[2-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amino]-6-(methyloxy)-3-pyridinyl]glycinate (672.0 g, 83%) as a dark oil.

1. customthe reaction was quenched in H2O (10 L)
2. customthen partitioned with EtOAc (10 L)
3. customThe layers were separated
4. extractionthe aqueous was extracted with EtOAc (7 L)
5. washwashed with H2O (7 L) and brine (7 L)
6. dry with materialdried over MgSO4 (1 kg)
7. filtrationfiltered
8. customevaporated
9. customThe resulting dark oil (853 g) was purified by column chromatography (9 kg silica, mixtures of heptane and EtOAc as eluent)