反应 #62022

反应方程式

5-(4-Isopropyl-piperazine-1-carbonyl)-furan-2-carbaldehyde

Vilsmeier reagent

1-isopropyl-piperizine dihydrochloride

5-formyl-2-furancarboxylic acid

→

desired product

收率 87.0%

(4-Isopropyl-piperazin-1-yl)-(5-piperidin-1-ylmethyl-furan-2-yl)-methanone

收率 87.0%

溶剂

DCM

DCM

反应条件

后处理

1. 1
   workup.STIRRINGthe combined mixture was stirred at 0° C. for 30 min
2. 2
   温度The mixture was warmed to rt
3. 3
   workup.STIRRINGstirred for another 1.5 h
4. 4
   过滤filtered
5. 5
   workup.ADDITIONThe filtrate (containing 5-formyl-furan-2-carbonyl chloride)
6. 6
   温度maintained at 0° C
7. 7
   温度was warmed to rt
8. 8
   workup.STIRRINGstirred for 30 min
9. 9
   过滤The reaction mixture was filtered
10. 10
    温度the filtrate was cooled to 0° C
11. 11
    workup.ADDITIONThis second filtrate was then treated dropwise with the previously prepared solution of 5-formyl-furan-2-carbonyl chloride at 0° C
12. 12
    workup.STIRRINGThe combined mixture was stirred at 0° C. for 30 min
13. 13
    温度The reaction mixture was cooled to 0° C.
14. 14
    过滤filtered
15. 15
    洗涤the filtrate was washed with H2O (2×15 mL), 0.5 N NaOH (1×15 mL)
16. 16
    其他The organic layer was separated
17. 17
    干燥dried over anhydrous Na2SO4
18. 18
    过滤filtered
19. 19
    浓缩concentrated

实验过程

5-(4-Isopropyl-piperazine-1-carbonyl)-furan-2-carbaldehyde. Vilsmeier reagent [(chloromethylene)dimethylammonium chloride, 0.820 g, 6.43 mmol] was suspended in DCM (30 mL) under nitrogen with stirring and cooled to 0° C. To this suspension was added 5-formyl-2-furancarboxylic acid (0.900 g, 6.43 mmol) and the combined mixture was stirred at 0° C. for 30 min. The mixture was warmed to rt, stirred for another 1.5 h, and filtered. The filtrate (containing 5-formyl-furan-2-carbonyl chloride) was set aside and maintained at 0° C. In a second flask, 1-isopropyl-piperizine dihydrochloride (1.28 g, 6.37 mmol) in DCM (15 mL) was cooled to 0° C. The solution was treated with TEA (2.250 g, 22.30 mmol) slowly and then was warmed to rt and stirred for 30 min. The reaction mixture was filtered and the filtrate was cooled to 0° C. This second filtrate was then treated dropwise with the previously prepared solution of 5-formyl-furan-2-carbonyl chloride at 0° C. The combined mixture was stirred at 0° C. for 30 min and then at rt for 1 h. The reaction mixture was cooled to 0° C. and filtered, and the filtrate was washed with H2O (2×15 mL), 0.5 N NaOH (1×15 mL), and satd. aq. NaCl (1×15 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated to yield the desired product (1.40 g, 87%).

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