Reaktion #53763

Reaktionsgleichung

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

Ausbeute 78.5%

Lösungsmittel

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeIn 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
   Temperaturat reflux over about one hour
4. 4
   workup.ALIQUOTThe reaction mixture was sampled at 1 and 2 hours at about 60° C. (
5. 5
   Sonstigeresulting in 90 and 91% area
6. 6
   SonstigeAfter 2 hours the resulting reaction mixture
7. 7
   Temperaturwas cooled
8. 8
   Einengenconcentrated 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
    Sonstigethe quenched solution below 30° C
12. 12
    SonstigeThe aqueous layer was removed
13. 13
    WaschenThe organic layer washed one time with 50 mL of 1.0 N HCl solution
14. 14
    SonstigeThe aqueous layer was removed
15. 15
    Waschenthe organic layer washed one time with 50 mL of water
16. 16
    Trocknendried over magnesium sulfate
17. 17
    Filtrationfiltered
18. 18
    Einengenconcentrated
19. 19
    SonstigeThis resulted in a gel-like solid residue
20. 20
    SonstigeThe ethyl acetate was removed on the roto-evaporator
21. 21
    Filtrationfiltered
22. 22
    Waschenrinsed with 50 mL of cold hexane
23. 23
    Sonstigedried under vacuum for about 1 to 2 hours

Vorschrift

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).

Quelle