反应详情

A 500 mL round bottom flask was charged with crude pyridine 33 (8.20 g, 27.7 mmol), acetone (300 mL), and O-methyloxime 30 (6.8 g, 27.7 mmol), and the reaction mixture was allowed to stir at room temperature for 12 hours, after which thin-layer chromatography testing suggested that pyridinyl salt formation was complete. The reaction was then concentrated under reduced pressure in a 500 mL round bottom flask, and charged with methanol (200 mL), additional pyridinyl salt prepared previously (600 mg), and potassium tert-butoxide (3.90 g, 34.6 mmol). The resulting mixture was heated to 65° C. for 4 hours. The reaction mixture was then poured into 400 mL of an aqueous solution saturated with NaHCO3 and extracted with 3×250 mL of methylene chloride. The organic fractions were pooled, dried over Na2SO4, filtered, concentrated under reduced pressure, then dissolved in a minimum volume of CH2Cl2, then loaded onto 3×40 g Isco RediSep normal phase silica cartridges, and purified on an Isco OptiX10 CombiFlash instrument using a gradient that started at 100% methylene chloride and ended at 90% methylene chloride, 9% methanol, and 1% concentrated ammonium hydroxide. Fractions containing the desired product were pooled and concentrated under reduced pressure; fractions containing impure product were pooled, concentrated under reduced pressure, then dissolved in a minimum volume of CH2Cl2, and loaded onto 2×40 g Isco RediSep normal phase silica cartridges, and purified on an Isco OptiX10 CombiFlash instrument using a gradient which started at 100% heptane and ended at 100% ethyl acetate. This process was repeated once on the remaining impure product. Yield of 34: 3.10 g (26%). 1H NMR (500 MHz, CDCl3) δ 1.50 (m, 2H), 1.76 (m, 2H), 2.55 (m, 1H), 2.77 (bs, 2H), 4.45 (bs, 2H), 5.04 (s, 2H), 6.48 (d, J=5.3 Hz, 1H), 6.96 (t, J=8.8 Hz, 2H), 7.24 (m, 6H), 7.57 (s, 1H), 7.76 (m, 2H), 7.86 (d, J=7.1 Hz, 1H). MS (ESI+) 430.2.

1. concentrationThe reaction was then concentrated under reduced pressure in a 500 mL round bottom flask
2. additioncharged with methanol (200 mL), additional pyridinyl salt
3. temperatureThe resulting mixture was heated to 65° C. for 4 hours
4. extractionextracted with 3×250 mL of methylene chloride
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutiondissolved in a minimum volume of CH2Cl2
9. custompurified on an Isco OptiX10 CombiFlash instrument
10. additionFractions containing the desired product
11. concentrationconcentrated under reduced pressure
12. additionfractions containing impure product
13. concentrationconcentrated under reduced pressure
14. dissolutiondissolved in a minimum volume of CH2Cl2
15. custompurified on an Isco OptiX10 CombiFlash instrument