反应详情

To a stirred suspension of methyl 2-amino-6-chloro-3-pyridinecarboxylate (2 g, 10.72 mmol) and sodium bicarbonate (900 mg, 10.72 mmol) in a mixture of methanol (40 mL) and water (20 mL) was added chloroacetaldehyde (50% wt. solution in water, 2.9 mL, 22.51 mmol). The resultant mixture was heated at reflux for 5 hours when more chloroacetaldehyde (50% wt. solution in water, 1.45 mL, 11.25 mmol) was added and heating at reflux continued for 16 hours. The majority of the solvent was then removed in vacuo and the residue was partitioned between ethyl acetate (150 mL) and saturated aqueous sodium bicarbonate (150 mL). The organic phase was separated and the aqueous phase was back extracted with ethyl acetate (150 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in DCM and purified on a silica cartridge (100 g) using a 0-100% ethyl acetate-cyclohexane+0-20% methanol gradient over 60 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (1.32 g).

1. additionwas added
2. temperatureheating
3. temperatureat reflux
4. customThe majority of the solvent was then removed in vacuo
5. customthe residue was partitioned between ethyl acetate (150 mL) and saturated aqueous sodium bicarbonate (150 mL)
6. customThe organic phase was separated
7. extractionthe aqueous phase was back extracted with ethyl acetate (150 mL)
8. dry with materialThe combined organic extracts were dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. dissolutionThe residue was dissolved in DCM
12. custompurified on a silica cartridge (100 g)
13. waitgradient over 60 mins
14. customevaporated in vacuo