Réaction #7753

Équation de réaction

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

Rendement 91.0%

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

Rendement 91.0%

Solvants

dichloromethane

dichloromethane

Conditions de réaction

Traitement

1. 1
   AutreThe cold bath is removed
2. 2
   Températureto warm to room temperature
3. 3
   workup.STIRRINGAfter stirring for 5 minutes
4. 4
   Températuremaintained at 0° C
5. 5
   workup.STIRRINGto stir
6. 6
   Températuregradually warm to room temperature over 12 hours
7. 7
   LavageThe 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
   Lavagethe combined organic layers washed with brine
10. 10
    Autredried
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated in vacuo
13. 13
    AutreThe crude product is purified over silica (2:1 to 1:1 hexane/ethyl acetate)

Mode opératoire

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