反应详情

To a dry solution of N-(6-chloropyridin-2-yl)-2,2-dimethyl propionamide (Preparation 107, 8.0 g, 37.6 mmol) in THF (120 mL), cooled to −78° C., was added dropwise, a solution of tert-butyllithium in pentane (1.7M, 48.7 mL, 82.8 mmol) over 40 min. The reaction was stirred at —78° C. for 3 h before adding a solution of iodine (11.46 g, 45.1 mmol) in THF (40 mL) dropwise. The mixture was brought up to rt and stirred for 16 h. 2M HCl (3 mL) was added to the reaction, and after 20 min the solvent was removed in vacuo. Crude material was partitioned between ethyl acetate (200 mL) and water (150 mL). Organics were separated and washed with 10% sodium thiosulfate solution (4×100 mL) then NaHCO3 solution (2×100 mL), dried (MgSO4) and the solvent removed in vacuo. The residue was purified by column chromatography (SiO2, CH2Cl2) to give the title compound. m/z (ES+)=338.93 [M+H]+.

1. additionwas added dropwise
2. customwas brought up to rt
3. stirringstirred for 16 h
4. customafter 20 min the solvent was removed in vacuo
5. customCrude material was partitioned between ethyl acetate (200 mL) and water (150 mL)
6. customOrganics were separated
7. washwashed with 10% sodium thiosulfate solution (4×100 mL)
8. dry with materialNaHCO3 solution (2×100 mL), dried (MgSO4)
9. customthe solvent removed in vacuo
10. customThe residue was purified by column chromatography (SiO2, CH2Cl2)