反应详情

A suspension of sodium hydride (60% in oil, 11.54 mmol) in THF (2 mL) was added to tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.59 g, 8.46 mmol) in THF (15 mL) at 0° C. Once the bubbling had subsided, a solution of 2-fluoro-4-methyl-5-nitropyridine (1.2 g, 7.69 mmol) in THF (3 mL) was added over 5 minutes. After 1 h, more sodium hydride (60% in oil, 0.15 g) was added. After a further 1 h, the reaction was quenched with aqueous ammonium chloride solution and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over sodium sulfate and concentrated to give a yellow solid. Purification by column chromatography (silica gel: 100-200 mesh, 1:4 EtOAc:heptane) yielded the title compound (1.62 g, 65%) as a yellow solid. LCMS (ES+) 323.3 (M+H)+, RT 1.71 minutes (method 4).

1. waitAfter a further 1 h
2. customthe reaction was quenched with aqueous ammonium chloride solution
3. extractionextracted with EtOAc (3×20 mL)
4. dry with materialThe combined organic extracts were dried over sodium sulfate
5. concentrationconcentrated
6. customto give a yellow solid
7. customPurification by column chromatography (silica gel: 100-200 mesh, 1:4 EtOAc:heptane)