반응 #53763

반응 방정식

t-BuMgCl THF

tert-butylmagnesium chloride

Methyl-(R)-3-(2′-bromo-1′-oxooctyloxy)tetradecanoate

→

(6R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-pyran-2-one

수율 78.5%

용매

ethyl acetate

반응 조건

후처리

1. 1
   기타In a 500 mL 3-necked round bottom flask fitted with a Claisen head with N2 inlet
2. 2
   workup.ADDITIONwere added to an addition funnel
3. 3
   온도at reflux over about one hour
4. 4
   workup.ALIQUOTThe reaction mixture was sampled at 1 and 2 hours at about 60° C. (
5. 5
   기타resulting in 90 and 91% area
6. 6
   기타After 2 hours the resulting reaction mixture
7. 7
   온도was cooled
8. 8
   농축concentrated on a roto-evaporator to about ⅓
9. 9
   workup.ADDITIONor mixtures thereof) and added to a mixture
10. 10
    workup.ADDITIONcontaining 250 mL of toluene, 75 mL of 10% HCl in a 1 L
11. 11
    기타the quenched solution below 30° C
12. 12
    기타The aqueous layer was removed
13. 13
    세척The organic layer washed one time with 50 mL of 1.0 N HCl solution
14. 14
    기타The aqueous layer was removed
15. 15
    세척the organic layer washed one time with 50 mL of water
16. 16
    건조dried over magnesium sulfate
17. 17
    여과filtered
18. 18
    농축concentrated
19. 19
    기타This resulted in a gel-like solid residue
20. 20
    기타The ethyl acetate was removed on the roto-evaporator
21. 21
    여과filtered
22. 22
    세척rinsed with 50 mL of cold hexane
23. 23
    기타dried under vacuum for about 1 to 2 hours

실험 절차

In a 500 mL 3-necked round bottom flask fitted with a Claisen head with N2 inlet, a West condenser, a thermocouple-J-KEM controller and an addition funnel was added a solution of tert-butylmagnesium chloride (341 mL of a 1.0 M solution, 341 mmole, 3 equiv.) at about 60° C. Methyl-(R)-3-(2′-bromo-1′-oxooctyloxy)tetradecanoate (52.6.0 g, 113.5 mmole, 1 equiv.) (“bromodiester”) and 25 mL of dry THE were added to an addition funnel. The bromodiester mixture was slowly added to the t-BuMgCl/THF mixture at reflux over about one hour. The reaction mixture was sampled at 1 and 2 hours at about 60° C. (resulting in 90 and 91% area normalized gas chromatography (AN GC) analysis, respectively). After 2 hours the resulting reaction mixture was cooled and concentrated on a roto-evaporator to about ⅓ to about ½ the original volume. The resulting syrupy mixture was taken up in about 250 mL of toluene (or an ether, such as methyl tert-butyl ether and the like; a hydrocarbon, such as hexane, heptane, and the like; or mixtures thereof) and added to a mixture containing 250 mL of toluene, 75 mL of 10% HCl in a 1 L jacketed flask keeping the quenched solution below 30° C. The aqueous layer was removed. The organic layer washed one time with 50 mL of 1.0 N HCl solution. The aqueous layer was removed, the organic layer washed one time with 50 mL of water, dried over magnesium sulfate, filtered and concentrated. This resulted in a gel-like solid residue. The residue was dissolved in 250 mL of ethyl acetate at 40° C. The ethyl acetate was removed on the roto-evaporator. The resulting crude off-white solid (42.4 g) was slurried up in about 100 mL of hexane and cooled to 0° C., filtered and rinsed with 50 mL of cold hexane followed by another 25 mL of cold hexane. The isolated white solids were air dried under vacuum for about 1 to 2 hours resulting in 31.4 g of (6R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-pyran-2-one (78.4% yield).

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