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

Temperatur

0 °C

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.

1. customThe cold bath is removed
2. temperatureto warm to room temperature
3. stirringAfter stirring for 5 minutes
4. temperaturemaintained at 0° C
5. stirringto stir
6. temperaturegradually warm to room temperature over 12 hours
7. washThe reaction is washed with a 5% aqueous solution of Na2CO3 (2×50 mL)
8. extractionThe combined aqueous layers are extracted several times with dichloromethane (50 mL)
9. washthe combined organic layers washed with brine
10. customdried
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude product is purified over silica (2:1 to 1:1 hexane/ethyl acetate)

ORD-Eintrag

ord-f90d2720f8ab4db0acb19cb4e25d4cad

Quelldatensatz

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06960593B2