反应详情

Sodium hydride (0.24 g, 6.05 mmol, 60% mineral oil dispersion) is added to a solution of [2-oxopyrrolidin-3(S)-yl]-carbamic acid tert-butyl ester (1.18 g, 5.89 mmol) in THF/DMF (62 mL, 9/1, v/v) at 0° C. The mixture is stirred for 2 minutes, then a solution of 7-bromomethyl-1-chloro-isoquinoline (1.4 g, 5.46 mmol) in THF (10 mL) is added dropwise via a cannula. The resulting yellow solution is stirred for 1 hour at 0° C. then at room temperature for 3 hours. The reaction mixture is quenched with saturated ammonium chloride solution, then diluted with EtOAc. The organic layer is washed with water and brine, then dried over MgSO4, filtered and concentrated. The residue is purified by column chromatography eluting with a gradient of 50% EtOAc/hexanes to 70% EtOAc/hexanes to give the product (1.67 g, 4.44 mmol) as a foamy white solid.

1. customat 0° C
2. stirringThe resulting yellow solution is stirred for 1 hour at 0° C.
3. waitat room temperature for 3 hours
4. customThe reaction mixture is quenched with saturated ammonium chloride solution
5. additiondiluted with EtOAc
6. washThe organic layer is washed with water and brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue is purified by column chromatography
11. washeluting with a gradient of 50% EtOAc/hexanes to 70% EtOAc/hexanes