반응 #733792

반응 방정식

n-butyllithium

hexane

2-bromomesitylene

4-(2-ethyl-[1,3]dioxan-2-yl)-2-methoxy-pyridine

DMF

→

title compound

수율 67.9%

4-(2-ethyl-[1,3]dioxan-2-yl)-2-methoxy-pyridine-3-carbaldehyde

수율 67.9%

용매

THF

THF

반응 조건

후처리

1. 1
   기타At −10° C.
2. 2
   workup.WAITwas continued for an additional hour at 0° C
3. 3
   온도The solution was cooled to −10° C.
4. 4
   온도to warm to 10° C. within 2.5 h
5. 5
   기타The cooling bath was then removed
6. 6
   workup.STIRRINGstirring
7. 7
   workup.WAITwas continued at room temperature for an additional hour
8. 8
   온도The clear brown solution was then cooled to −23° C.
9. 9
   온도to slowly warm up to room temperature overnight
10. 10
    기타The reaction was quenched by addition of 100 mL saturated aqueous NH4Cl
11. 11
    workup.ADDITION50 mL water were added
12. 12
    추출The mixture was extracted three times with 150 mL
13. 13
    세척The combined organic phases were washed two times with 300 mL
14. 14
    건조in total 600 mL brine, dried over 20 g Na2SO4 (30 min)
15. 15
    여과filtered
16. 16
    세척The filter cake was washed with 40 mL TBME
17. 17
    기타After evaporation of solvent
18. 18
    기타in a rotary evaporator (40° C./10 mbar)
19. 19
    기타the crude product (12.048 g, 214% by weight) was obtained as a brown oil which
20. 20
    여과was then purified by silica gel filtration (97 g silica gel)
21. 21
    세척a gradient elution with 2.0 L heptane/ethyl acetate (30:1) and 1.4 L heptane/ethyl acetate (5:1)
22. 22
    기타Evaporation to dryness of the second fraction
23. 23
    기타in a rotary evaporator (40° C./10 mbar)

실험 절차

A stirred solution of 6.87 mL 2-bromomesitylene (44.78 mmol, 2.0 eq) in 44 mL THF was cooled to −45° C. 35.8 mL n-butyllithium in hexane (2.5 M, 89.56 mmol, 4.0 eq) were added within 20 min. The resulting white suspension was then allowed to warm to 0° C. within 2.5 h. At −10° C. the reaction mixture became a clear solution. Stirring was continued for an additional hour at 0° C. The solution was cooled to −10° C. and a solution of 5.00 g 4-(2-ethyl-[1,3]dioxan-2-yl)-2-methoxy-pyridine (22.39 mmol), as obtainable from Example 3, in 15 mL THF was added over 15 min under vigorous stirring. The resulting brown suspension was allowed to warm to 10° C. within 2.5 h. The cooling bath was then removed and stirring was continued at room temperature for an additional hour. The clear brown solution was then cooled to −23° C. and 5.19 mL DMF (67.17 mmol, 3.0 eq) were added. The mixture was allowed to slowly warm up to room temperature overnight. The reaction was quenched by addition of 100 mL saturated aqueous NH4Cl. After 15 min, 50 mL water were added. The mixture was extracted three times with 150 mL, in total with 450 mL TBME. The combined organic phases were washed two times with 300 mL, in total 600 mL brine, dried over 20 g Na2SO4 (30 min) and filtered. The filter cake was washed with 40 mL TBME. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (12.048 g, 214% by weight) was obtained as a brown oil which was then purified by silica gel filtration (97 g silica gel) using a gradient elution with 2.0 L heptane/ethyl acetate (30:1) and 1.4 L heptane/ethyl acetate (5:1). Evaporation to dryness of the second fraction in a rotary evaporator (40° C./10 mbar) yielded the title compound (3.832 g, 15.2 mmol, 68% by weight).

출처