反应 #7753

反应方程式

1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrogen chloride

triethylamine

4-(2,2-Dimethylpropionyloxy)-pyrazolidine-1-carboxylic acid 1-benzyl ester

4-Fluorophenylacetic acid

→

desired product

收率 91.0%

2-[2-(4-fluorophenyl)acetyl]-4-(2,2-dimethylpropionyloxy)-pyrazolidine-1-carboxylic acid 1-benzyl ester

收率 91.0%

溶剂

dichloromethane

dichloromethane

反应条件

后处理

1. 1
   其他The cold bath is removed
2. 2
   温度to warm to room temperature
3. 3
   workup.STIRRINGAfter stirring for 5 minutes
4. 4
   温度maintained at 0° C
5. 5
   workup.STIRRINGto stir
6. 6
   温度gradually warm to room temperature over 12 hours
7. 7
   洗涤The reaction is washed with a 5% aqueous solution of Na2CO3 (2×50 mL)
8. 8
   萃取The combined aqueous layers are extracted several times with dichloromethane (50 mL)
9. 9
   洗涤the combined organic layers washed with brine
10. 10
    其他dried
11. 11
    过滤filtered
12. 12
    浓缩concentrated in vacuo
13. 13
    其他The crude product is purified over silica (2:1 to 1:1 hexane/ethyl acetate)

实验过程

4-(2,2-Dimethylpropionyloxy)-pyrazolidine-1-carboxylic acid 1-benzyl ester, 30, (1.45 g, 4.23 mmol) is dissolved in dichloromethane (21 mL). The solution is cooled to 0° C. and triethylamine (1.30 mL, 9.31 mmol) added dropwise via syringe. The cold bath is removed and the reaction allowed to warm to room temperature and continue stirring 20 minutes. 4-Fluorophenylacetic acid (848 mg, 5.50 mmol) is added. After stirring for 5 minutes, the reaction mixture is transferred via cannula into a solution of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrogen chloride in dichloromethane (21 mL) maintained at 0° C. The reaction is allowed to stir and gradually warm to room temperature over 12 hours. The reaction is washed with a 5% aqueous solution of Na2CO3 (2×50 mL). The combined aqueous layers are extracted several times with dichloromethane (50 mL) and the combined organic layers washed with brine, dried, filtered and concentrated in vacuo. The crude product is purified over silica (2:1 to 1:1 hexane/ethyl acetate) to afford 1.71 g (91% yield) of the desired product as a white solid.

来源