反应详情

Ozone was bubbled through a cooled (−78° C.) solution of methyl 3-(propan-2-yloxy)-2-(prop-2-en-1-yloxy)benzoate (123d, 438.1 mg, 1.75 mmol) in dichloromethane (17.5 mL) until a persistent violet-blue color was obtained (about 5 minutes). Nitrogen was bubbled into the solution for 3 minutes, causing the color to fade, then dimethyl sulfide (1.0 mL, 13.5 mmol) was added and the mixture allowed to warm to room temperature for one hour. The solvents were evaporated and the residue partitioned between sodium carbonate solution (sat., aq., 10 mL) and ethyl acetate (2×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under vacuum to give the crude residue. This crude aldehyde was dissolved in methanol (10.0 mL) and treated with 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one hydrochloride (Cpd V, 334 mg, 1.87 mmol) at room temperature for five minutes, then sodium cyanoborohydride (332 mg, 4.50 mmol) was added and the mixture stirred at room temperature for 14.5 hours. The solvents were evaporated under vacuum and the residue partitioned between deionized water (10 mL) and ethyl acetate (2×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered, concentrated under vacuum, and purified by column chromatography (EtOH+5% NH4OH in ethyl acetate) to give methyl 2-(2-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]amino}ethoxy)-3-(propan-2-yloxy)benzoate (123e, 76 mg, 11% yield) as a colorless glass.

1. customOzone was bubbled through
2. customwas obtained (about 5 minutes)
3. customNitrogen was bubbled into the solution for 3 minutes
4. customThe solvents were evaporated
5. customthe residue partitioned between sodium carbonate solution (sat., aq., 10 mL) and ethyl acetate (2×20 mL)
6. dry with materialThe combined organic extracts were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customto give the crude residue
10. customThe solvents were evaporated under vacuum
11. customthe residue partitioned between deionized water (10 mL) and ethyl acetate (2×20 mL)
12. dry with materialThe combined organic extracts were dried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated under vacuum
15. custompurified by column chromatography (EtOH+5% NH4OH in ethyl acetate)