تفاعل #1121760

معادلة التفاعل

tert-butyldimethylchlorosilane

2-naphthol

1,3-dicyclohexylcarbodiimide

Imidazole

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

→

titled compound

المردود 48.4%

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

المردود 48.4%

المذيبات

dichloromethane

dichloromethane

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   أخرىpurged flask
2. 2
   درجة الحرارةto warm to room temperature
3. 3
   ترشيحAfter filtration
4. 4
   غسيلthe filtrate was washed with a saturated sodium bicarbonate solution
5. 5
   تجفيفa brine solution, respectively, dried over anhydrous magnesium sulfate
6. 6
   ترشيحfiltered
7. 7
   أخرىevaporated to dryness
8. 8
   workup.STIRRINGstirred at room temperature
9. 9
   درجة الحرارةThe pH of the solution was maintained by 1N sodium hydroxide solution
10. 10
    أخرىfinally adjusted to 7.0 upon completion of the reaction
11. 11
    أخرىthe Lipase was removed by filtration
12. 12
    استخلاصThe reaction mixture was extracted with 50 ml of toluene twice
13. 13
    استخلاصThe aqueous layer was extracted twice again
14. 14
    تجفيفdried over anhydrous magnesium sulfate
15. 15
    ترشيحfiltered
16. 16
    تركيزconcentrated
17. 17
    workup.STIRRINGThe reaction mixture was stirred at room temperatures for about 4 hours
18. 18
    ترشيحThe precipitate was filtered off
19. 19
    غسيلThe filtrate was washed with a saturated sodium bicarbonate solution
20. 20
    تجفيفdried over anhydrous magnesium sulfate
21. 21
    ترشيحfiltered
22. 22
    أخرىevaporated under vacuum
23. 23
    أخرىThe residue was purified by flash chromatography on silica gel

الإجراء التجريبي

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%).

المصدر