反应详情

温度

0 °C

To a solution of 5-chloro-2-fluoropyridine (0.5 g, 3.8 mmol, Eq: 1.00) and 1-tert-butyl 3-methyl azetidine-1,3-dicarboxylate (818 mg, 3.8 mmol, Eq: 1.00) in toluene (5 ml) was added dropwise at 0° C. for 15 min a 0.5 M solution of KHMDS (7.6 ml, 3.8 mmol, Eq: 1.00) in toluene. The colorless solution turned into yellow-orange. After stirring at 0° C. for 45 min, the reaction mixture was allowed to warm to 20° C. and stirred for 2.5 h. A saturated aqueous NH4Cl solution (50 ml) was added and the aqueous phase was extracted with AcOEt (2×75 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, 12 g, 10% to 60% AcOEt in heptane) to yield a colorless gum (0.234 g; 19%). m/z=327.2 [M+H]+.

1. temperatureto warm to 20° C.
2. stirringstirred for 2.5 h
3. extractionthe aqueous phase was extracted with AcOEt (2×75 ml)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude material was purified by flash chromatography (silica gel, 12 g, 10% to 60% AcOEt in heptane)
9. customto yield a colorless gum (0.234 g; 19%)