Réaction #1121760

Équation de réaction

tert-butyldimethylchlorosilane

2-naphthol

1,3-dicyclohexylcarbodiimide

Imidazole

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

→

titled compound

Rendement 48.4%

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

Rendement 48.4%

Solvants

dichloromethane

dichloromethane

ethyl acetate

Conditions de réaction

Traitement

1. 1
   Autrepurged flask
2. 2
   Températureto warm to room temperature
3. 3
   FiltrationAfter filtration
4. 4
   Lavagethe filtrate was washed with a saturated sodium bicarbonate solution
5. 5
   Séchagea brine solution, respectively, dried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Autreevaporated to dryness
8. 8
   workup.STIRRINGstirred at room temperature
9. 9
   TempératureThe pH of the solution was maintained by 1N sodium hydroxide solution
10. 10
    Autrefinally adjusted to 7.0 upon completion of the reaction
11. 11
    Autrethe Lipase was removed by filtration
12. 12
    ExtractionThe reaction mixture was extracted with 50 ml of toluene twice
13. 13
    ExtractionThe aqueous layer was extracted twice again
14. 14
    Séchagedried over anhydrous magnesium sulfate
15. 15
    Filtrationfiltered
16. 16
    Concentrationconcentrated
17. 17
    workup.STIRRINGThe reaction mixture was stirred at room temperatures for about 4 hours
18. 18
    FiltrationThe precipitate was filtered off
19. 19
    LavageThe filtrate was washed with a saturated sodium bicarbonate solution
20. 20
    Séchagedried over anhydrous magnesium sulfate
21. 21
    Filtrationfiltered
22. 22
    Autreevaporated under vacuum
23. 23
    AutreThe residue was purified by flash chromatography on silica gel

Mode opératoire

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%).

Source