反应详情

A dry 1 L round bottomed flask was charged with anhydrous Et2O (500 mL) and cooled to 0° C. (ice-water bath). After having been rinsed with hexane, NaH (60% w/w suspension in mineral oil, 16 g, 400 mmol, 2 eq, weight before rinsing) was added followed by absolute EtOH (23.2 mL, 400 moles, 2 eq). After 10 minutes, a mixture of 3-pyridine carboxaldehyde (18.8 mL, 200 mmol, 1 eq) and N,N-dimethyl glycine ethyl ester (84.8 mL, 3 eq) (N,N-dimethyl glycine methyl ester also performs satisfactorily in this preparation) was added during 1 minute. This mixture was as stirred overnight at room temperature, heated at 30° C. for 1 h, and then transferred to a 2 L separation funnel. The mixture was diluted with EtOAc (500 mL) and H20 (500 mL) and the organic phase was transferred to a beaker and stirred with 1N HCl (500 mL) at room temperature for 10 minutes. The mixture was checked to confirm a pH=1 and then the phases were separated. The aqueous layer was retained and slowly neutralized by the addition of solid NaHCO3. This solution was extracted with EtOAc (3×300 mL), the combined extracts dried (Na2SO4), filtered and concentrated to a yellow solid. Crystallization from EtOAc-Hexanes (4:1) provided 20.0 g (52% yield) of pale yellow 8. RP-HPLC Method 2-100% B.

1. additionwas added
2. customalso performs satisfactorily in this preparation)
3. additionwas added during 1 minute
4. temperatureheated at 30° C. for 1 h
5. customtransferred to a 2 L separation funnel
6. additionThe mixture was diluted with EtOAc (500 mL) and H20 (500 mL)
7. stirringstirred with 1N HCl (500 mL) at room temperature for 10 minutes
8. customthe phases were separated
9. additionslowly neutralized by the addition of solid NaHCO3
10. extractionThis solution was extracted with EtOAc (3×300 mL)
11. dry with materialthe combined extracts dried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated to a yellow solid
14. customCrystallization from EtOAc-Hexanes (4:1)
15. customprovided 20.0 g (52% yield) of pale yellow 8