反应 #1432

反应方程式

1-bromo-4-chlorobutane

cyclopentanecarboxylic acid

diisopropylamine

n-butyl lithium

→

lithium diisopropylamide

title product

1-(4-Chlorobutyl)cyclopentanecarboxylic acid

溶剂

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

反应条件

后处理

1. 1
   温度maintaining the temperature between -3° C.-1° C
2. 2
   workup.WAITAfter an additional 15 minutes at 0° C.
3. 3
   其他the bath was removed
4. 4
   workup.STIRRINGthe reaction stirred 15 minutes more
5. 5
   其他to rise to 11° C
6. 6
   其他rising to -66° C
7. 7
   workup.WAITAfter 16 hours
8. 8
   温度to warm to room temperature in situ
9. 9
   其他The reaction was quenched with methanol (10 ml.)
10. 10
    浓缩concentrated in vacuo
11. 11
    其他The residue was partitioned between water (200 ml.) and ethyl ether (200 ml.)
12. 12
    萃取extracted with methylene chloride (3×150 ml.)
13. 13
    干燥dried (magnesium sulfate)
14. 14
    过滤filtered
15. 15
    其他evaporated
16. 16
    其他to give 20.0 g

实验过程

A solution of lithium diisopropylamide was prepared under nitrogen from diisopropylamine (31.0 ml., 220 mmol.) and n-butyl lithium (1.5M in hexane, 88.0 ml., 220 mmol.) in tetrahydrofuran (80 ml.), maintaining the temperature between -3° C.-1° C. After stirring 15 minutes, cyclopentanecarboxylic acid (11.4 g., 100 mmol.) in tetrahydrofuran (10 ml.) was added at 0° C.-3° C. over 25 minutes. After an additional 15 minutes at 0° C., the bath was removed and the reaction stirred 15 minutes more, causing the temperature to rise to 11° C. The milky white solution was cooled to -74° C. and 1-bromo-4-chlorobutane (23 ml., 200 mmol.) in tetrahydrofuran was added quickly, the temperature rising to -66° C. After 16 hours, the reaction was allowed to warm to room temperature in situ. The reaction was quenched with methanol (10 ml.) and concentrated in vacuo. The residue was partitioned between water (200 ml.) and ethyl ether (200 ml.). The aqueous layer was acidified to pH 1 with 12M hydrochloric acid and extracted with methylene chloride (3×150 ml.), dried (magnesium sulfate), filtered and evaporated to give 20.0 g. of the title product as a yellow oil.

来源