反应 #1121760

反应方程式

tert-butyldimethylchlorosilane

2-naphthol

1,3-dicyclohexylcarbodiimide

Imidazole

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

→

titled compound

收率 48.4%

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

收率 48.4%

溶剂

dichloromethane

dichloromethane

ethyl acetate

反应条件

后处理

1. 1
   其他purged flask
2. 2
   温度to warm to room temperature
3. 3
   过滤After filtration
4. 4
   洗涤the filtrate was washed with a saturated sodium bicarbonate solution
5. 5
   干燥a brine solution, respectively, dried over anhydrous magnesium sulfate
6. 6
   过滤filtered
7. 7
   其他evaporated to dryness
8. 8
   workup.STIRRINGstirred at room temperature
9. 9
   温度The pH of the solution was maintained by 1N sodium hydroxide solution
10. 10
    其他finally adjusted to 7.0 upon completion of the reaction
11. 11
    其他the Lipase was removed by filtration
12. 12
    萃取The reaction mixture was extracted with 50 ml of toluene twice
13. 13
    萃取The aqueous layer was extracted twice again
14. 14
    干燥dried over anhydrous magnesium sulfate
15. 15
    过滤filtered
16. 16
    浓缩concentrated
17. 17
    workup.STIRRINGThe reaction mixture was stirred at room temperatures for about 4 hours
18. 18
    过滤The precipitate was filtered off
19. 19
    洗涤The filtrate was washed with a saturated sodium bicarbonate solution
20. 20
    干燥dried over anhydrous magnesium sulfate
21. 21
    过滤filtered
22. 22
    其他evaporated under vacuum
23. 23
    其他The residue was purified by flash chromatography on silica gel

实验过程

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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