Reaktion #50960

Reaktionsgleichung

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

Ausbeute 91.0%

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

Ausbeute 91.0%

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cold bath is removed
2. 2
   Temperaturto warm to room temperature
3. 3
   workup.STIRRINGAfter stirring for 5 minutes
4. 4
   Temperaturmaintained at 0° C
5. 5
   workup.STIRRINGto stir
6. 6
   Temperaturgradually warm to room temperature over 12 hours
7. 7
   WaschenThe reaction is washed with a 5% aqueous solution of Na2CO3 (2×50 mL)
8. 8
   ExtraktionThe combined aqueous layers are extracted several times with dichloromethane (50 mL)
9. 9
   Waschenthe combined organic layers washed with brine
10. 10
    Sonstigedried
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated in vacuo
13. 13
    SonstigeThe crude product is purified over silica (2:1 to 1:1 hexane/ethyl acetate)

Vorschrift

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.

Quelle