Reaction #7758

Reaction equation

2-[2-(4-Fluorophenyl)acetyl]-4-hydroxy-pyrazolidine-1-carboxylic acid benzyl ester

p-nitrophenyl chloroformate

pyridine

→

desired product

Yield 86.0%

2-[2-(4-fluorophenyl)acetyl]-4-(4-nitro-phenoxycarbonyloxy)-pyrazolidine-1-carboxylic acid benzyl ester

Yield 86.0%

Solvents

dichloromethane

water

Conditions

Workup

1. 1
   workup.STIRRINGStirring
2. 2
   workup.STIRRINGby stirring at room temperature for 12 hours
3. 3
   Extractionextracted with dichloromethane (40 mL)
4. 4
   WashThe organic layer is washed with 0.5 N NaOH (2×40 mL)
5. 5
   ExtractionThe combined aqueous layers are back-extracted
6. 6
   Extractionextracted with dichloromethane (30 mL)
7. 7
   WashThe combined organic layers are washed with brine (30 mL)
8. 8
   Otherdried
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated in vacuo
11. 11
    OtherThe crude material is purified over silica (3:1 to 2:1 to 1:1 hexane/ethyl acetate)

Procedure

2-[2-(4-Fluorophenyl)acetyl]-4-hydroxy-pyrazolidine-1-carboxylic acid benzyl ester, 38, (366 mg, 1.02 mmol) is dissolved in dichloromethane (10 mL). The solution is cooled to 0° C. and p-nitrophenyl chloroformate (411 mg, 2.04 mmol) is added in one portion. The solution is stirred at 0° C., and pyridine (198 μL, 2.45 mmol) added. Stirring is continued at 0° C. for 1 hour followed by stirring at room temperature for 12 hours. The reaction is diluted with water (40 mL) and extracted with dichloromethane (40 mL). The organic layer is washed with 0.5 N NaOH (2×40 mL). The combined aqueous layers are back-extracted extracted with dichloromethane (30 mL). The combined organic layers are washed with brine (30 mL), dried, filtered, and concentrated in vacuo. The crude material is purified over silica (3:1 to 2:1 to 1:1 hexane/ethyl acetate) to afford 462 mg (86% yield) of the desired product as a white foam.

Source