反応 #1121760

反応方程式

tert-butyldimethylchlorosilane

2-naphthol

1,3-dicyclohexylcarbodiimide

Imidazole

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

→

titled compound

収率 48.4%

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

収率 48.4%

溶媒

dichloromethane

dichloromethane

ethyl acetate

反応条件

後処理

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

実験手順

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%).

出典