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

HRID 22688

Reaction equation

HRID 22688 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([OH:16])[CH2:13][N:12]1[C:17](=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:28]([O:30][C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=1)=[O:29].N1C=CC=CC=1>ClCCl.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([O:16][C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[CH:35][CH:36]=2)=[O:29])[CH2:13][N:12]1[C:17](=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 821294-Nitrophenyl chloroformateHCID 207247442-[2-(4-Fluorophenyl)acetyl]-4-hydroxypyrazolidine-1-carboxylic acid benzyl ester

Product 1

HCID 207247432-[2-(4-Fluorophenyl)acetyl]-4-(4-nitro-phenoxycarbonyloxy)-pyrazolidine-1-carboxylic acid benzyl esterYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

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.

Workup

  1. stirringStirring
  2. stirringby stirring at room temperature for 12 hours
  3. extractionextracted with dichloromethane (40 mL)
  4. washThe organic layer is washed with 0.5 N NaOH (2×40 mL)
  5. extractionThe combined aqueous layers are back-extracted
  6. extractionextracted with dichloromethane (30 mL)
  7. washThe combined organic layers are washed with brine (30 mL)
  8. customdried
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material is purified over silica (3:1 to 2:1 to 1:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-230ad8afcb884784baa19701dbf60b48
Source dataset
uspto-grants-2005_02
Patent number
US06849627B2

Linked notes

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