反应详情

A solution of (2-oxopyrrolidin-3-(S)-yl)carbamic acid tert-butyl ester (1.56 g, 7.8 mmol) in 80 mL of THF:DMF (5:1) is treated with 5-bromomethylfuran-2-carbo-nitrile (3.23 g, 16 mmol) and sodium hydride (60%) (0.32 g, 8 mmol) as described in EXAMPLE 122, Part F. After addition, the solution is allowed to warm to ambient temperatures. After 5 hours, the solution is quenched by the addition of sat. NH4Cl. The solution is diluted with EtOAc and washed with H2O (3x) and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with gradient of 40% EtOAc/hexanes to 80% EtOAc/hexanes to afford [1-(5-cyanofuran-2-ylmethyl)-2-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester (2.38 g, 7.8 mmol) as a white solid. A portion of this material (1.28 g, 4.2 mmol) is treated as described in EXAMPLE 122, Part G to yield the title compound (1.1 g, 4.55 mmol).

1. additionAfter addition
2. temperatureto warm to ambient temperatures
3. customthe solution is quenched by the addition of sat. NH4Cl
4. additionThe solution is diluted with EtOAc
5. washwashed with H2O (3x) and saturated NaCl
6. dry with materialThe organic layer is dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product is purified by column chromatography
10. washeluting with gradient of 40% EtOAc/hexanes to 80% EtOAc/hexanes