Reaktion #1121760

Reaktionsgleichung

tert-butyldimethylchlorosilane

2-naphthol

1,3-dicyclohexylcarbodiimide

Imidazole

(R)-2-ethoxycarbonylmethyl-4-hydroxy-2-cyclopenten-1-one

→

titled compound

Ausbeute 48.4%

(R)-2-(2-Naphthoxycarbonylmethyl)-4-tert-butyldimethylsilyloxy-2-cyclopenten-1-one

Ausbeute 48.4%

Lösungsmittel

dichloromethane

dichloromethane

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigepurged flask
2. 2
   Temperaturto warm to room temperature
3. 3
   FiltrationAfter filtration
4. 4
   Waschenthe filtrate was washed with a saturated sodium bicarbonate solution
5. 5
   Trocknena brine solution, respectively, dried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated to dryness
8. 8
   workup.STIRRINGstirred at room temperature
9. 9
   TemperaturThe pH of the solution was maintained by 1N sodium hydroxide solution
10. 10
    Sonstigefinally adjusted to 7.0 upon completion of the reaction
11. 11
    Sonstigethe Lipase was removed by filtration
12. 12
    ExtraktionThe reaction mixture was extracted with 50 ml of toluene twice
13. 13
    ExtraktionThe aqueous layer was extracted twice again
14. 14
    Trocknendried over anhydrous magnesium sulfate
15. 15
    Filtrationfiltered
16. 16
    Einengenconcentrated
17. 17
    workup.STIRRINGThe reaction mixture was stirred at room temperatures for about 4 hours
18. 18
    FiltrationThe precipitate was filtered off
19. 19
    WaschenThe filtrate was washed with a saturated sodium bicarbonate solution
20. 20
    Trocknendried over anhydrous magnesium sulfate
21. 21
    Filtrationfiltered
22. 22
    Sonstigeevaporated under vacuum
23. 23
    SonstigeThe residue was purified by flash chromatography on silica gel

Vorschrift

5 g (27.1 mmol, 98% e.e.) of (R)-2-ethoxycarbonylmethyl-4-hydroxy-2-cyclopenten-1-one was dissolved in ethyl acetate and the solution was placed in a nitrogen-purged flask. Imidazole (2.77 g, 40.7 mmol) was added. The solution was cooled to 0° C. and tert-butyldimethylchlorosilane (5.3 g, 35 mmol) was added in portions. The reaction mixture was allowed to warm to room temperature, and stirred for 15 hours. After filtration, the filtrate was washed with a saturated sodium bicarbonate solution and a brine solution, respectively, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue and 1 g of Candida antartica lipase were suspended in 100 ml of phosphate buffer (10 mM, pH 6.5-7.5) and stirred at room temperature. The pH of the solution was maintained by 1N sodium hydroxide solution and finally adjusted to 7.0 upon completion of the reaction and the Lipase was removed by filtration. The reaction mixture was extracted with 50 ml of toluene twice. The pH of the aqueous layer was further adjusted to 6.0 using a saturated sodium hydrogensulfate solution. The aqueous layer was extracted twice again using 100 ml of ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue and 2-naphthol (5.0 g, 34.7 mmol) was dissolved in dichloromethane (50 ml), and 0.2 g 4-(dimethylamine)pyridine were added together to a 30 ml dichloromethane solution containing 1,3-dicyclohexylcarbodiimide (7.5 g, 36 mmol). The reaction mixture was stirred at room temperatures for about 4 hours. The precipitate was filtered off. The filtrate was washed with a saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered, and evaporated under vacuum. The residue was purified by flash chromatography on silica gel to give the titled compound as white solid (5.2 g, 48%).

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