Reaction #50960

Reaction equation

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

Yield 91.0%

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

Yield 91.0%

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   OtherThe cold bath is removed
2. 2
   Temperatureto warm to room temperature
3. 3
   workup.STIRRINGAfter stirring for 5 minutes
4. 4
   Temperaturemaintained at 0° C
5. 5
   workup.STIRRINGto stir
6. 6
   Temperaturegradually warm to room temperature over 12 hours
7. 7
   WashThe reaction is washed with a 5% aqueous solution of Na2CO3 (2×50 mL)
8. 8
   ExtractionThe combined aqueous layers are extracted several times with dichloromethane (50 mL)
9. 9
   Washthe combined organic layers washed with brine
10. 10
    Otherdried
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated in vacuo
13. 13
    OtherThe crude product is purified over silica (2:1 to 1:1 hexane/ethyl acetate)

Procedure

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.

Source