반응 #57413

반응 방정식

Heptane

DMF

NBS

Heptane

Dimethylformamide

tricyclo[3.3.1.13,7]decane-1-acetic acid

→

α-bromotricyclo[3.3.1.13,7]decane-1-acetic acid

수율 66.0%

용매

water

acetonitrile

Water

water

thionyl chloride

반응 조건

후처리

1. 1
   기타equipped with a condenser
2. 2
   workup.ADDITION0.3 mL was added
3. 3
   온도the reaction mixture was heated to 60° C
4. 4
   workup.STIRRINGThe reaction was stirred for 3 hours
5. 5
   온도while maintaining the temperature at 60 to 65° C
6. 6
   기타the completion of the reaction
7. 7
   workup.DISTILLATIONExcess thionyl chloride was distilled off at 78-80° C
8. 8
   workup.ADDITIONWater was then added cautiously
9. 9
   기타(violent reaction)
10. 10
    기타to quench
11. 11
    기타the reaction (total volume 1050 mL)
12. 12
    기타the aqueous layer was separated from the organic layer
13. 13
    세척The organic layer was washed with additional water (600 mL)
14. 14
    기타the aqueous layer was again separated from the organic layer
15. 15
    workup.ADDITIONAdditional water (150 mL) was added to the organic heptane layer
16. 16
    workup.DISTILLATIONthe heptane was distilled off from the aqueous layer
17. 17
    workup.DISTILLATIONAfter distilling off the heptane, tetrahydrofuran (THF;1200 mL)
18. 18
    workup.ADDITIONwas added to the aqueous layer
19. 19
    workup.STIRRINGthe resulting mixture was stirred vigorously at room temperature for 16 hours for slow hydrolysis
20. 20
    workup.ADDITIONAddition water (150 mL)
21. 21
    workup.ADDITIONwas then added
22. 22
    기타the hydrolysis
23. 23
    workup.DISTILLATIONThe THF was then distilled off
24. 24
    기타yielding
25. 25
    workup.ADDITIONSeeds were then added
26. 26
    기타to reach room temperature so that a heavy solid
27. 27
    workup.STIRRINGwas stirred for 2 hours at room temperature
28. 28
    여과The solid was then filtered off
29. 29
    세척washed with acetonitrile (2×250 mL)
30. 30
    기타264 grams with AP 95 in 66% yield after drying in vacuo at room temperature
31. 31
    기타The mother liquor (113 gram residue) was then triturated the residue with water and acetonitrile (250 mL/250 mL) for 1-2 hours at room temperature
32. 32
    여과The reaction was then filter
33. 33
    기타the solid dried

실험 절차

Solid tricyclo[3.3.1.13,7]decane-1-acetic acid (Formula N) (288 grams; 1.48 mole) was suspended in thionyl chloride (465 mL) in a 3-necked round bottomed flask, equipped with a condenser. Dimethylformamide (DMF;0.3 mL was added and the suspension was stirred at room temperature for 1.5 hours. Completion of the reaction was checked by gas chromatography. Solid NBS (307 g) was then added portionwise to the reaction mixture and the reaction mixture was heated to 60° C. The reaction was stirred for 3 hours while maintaining the temperature at 60 to 65° C. Monitoring by gas chromatography was performed to ensure the completion of the reaction. Heptane (900 mL) was added to the reaction mixture. Excess thionyl chloride was distilled off at 78-80° C. Water was then added cautiously (violent reaction) to quench the reaction (total volume 1050 mL). Heptane (500 mL) and water (600 mL) were then added and the aqueous layer was separated from the organic layer. The organic layer was washed with additional water (600 mL) and the aqueous layer was again separated from the organic layer. Additional water (150 mL) was added to the organic heptane layer and the heptane was distilled off from the aqueous layer. Specifically, 70 mL of water co-distilled with heptane. After distilling off the heptane, tetrahydrofuran (THF;1200 mL) was added to the aqueous layer and the resulting mixture was stirred vigorously at room temperature for 16 hours for slow hydrolysis. Monitoring via gas chromatography indicated the presence of some unreacted acid chloride. Addition water (150 mL) was then added to speed up the hydrolysis and the reaction was monitored by gas chromatography to ensure completion. The THF was then distilled off yielding a biphasic (water and oil) reaction mixture. Seeds were then added and the reaction was allowed to reach room temperature so that a heavy solid comes out. Water (250 mL) and acetonitrile (500 mL) were added to keep the suspension stirrable as the suspension was stirred for 2 hours at room temperature. The solid was then filtered off and washed with acetonitrile (2×250 mL). This filtrate contained the first crop of α-bromotricyclo[3.3.1.13,7]decane-1-acetic acid (Formula O); 264 grams with AP 95 in 66% yield after drying in vacuo at room temperature. The mother liquor (113 gram residue) was then triturated the residue with water and acetonitrile (250 mL/250 mL) for 1-2 hours at room temperature. The reaction was then filter and the solid dried to obtain a second crop of α-bromotricyclo[3.3.1.13,7]decane-1-acetic acid (Formula O); 64 grams with AP 90 in 16% yield.

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