Oxalyl chloride → 5-{[4-(2-tert-Butylphenyl)piperazin-1-yl]carbonyl}-1-phenylpyrrolidin-2-one

HRID 534956Notes

Reaction equation

HRID 534956 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C@H:5]([C:13]([OH:15])=O)[CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.Cl.Cl.[C:24]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)([CH3:27])([CH3:26])[CH3:25]>CN(C)C=O.O1CCCC1>[C:24]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N:34]1[CH2:39][CH2:38][N:37]([C:13]([CH:5]2[N:6]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:2](=[O:1])[CH2:3][CH2:4]2)=[O:15])[CH2:36][CH2:35]1)([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 42260557HCID 42260557, compoundHCID 667511491-(2-Tert-butylphenyl)piperazine dihydrochloride

Product 1

HCID 667928365-{[4-(2-tert-Butylphenyl)piperazin-1-yl]carbonyl}-1-phenylpyrrolidin-2-oneYield 62.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cold stirred solution of 5-oxo-1-phenylproline (Reference Example 12, 0.22 g, 1.08 mmol) and N,N-dimethylformamide (3 drops) in tetrahydrofuran (10 mL) was added oxalyl chloride (0.14 g, 1.10 mmol). The mixture was stirred at 0° C. for 30 min, and then allowed to warm to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in pyridine (10 mL). To this mixture was added 1-(2-tert-butylphenyl)piperazine dihydrochloride (Reference Example 1, 0.30 g, 1.03 mmol) and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and 10% NaHCO3 solution. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was dissolved in ethyl acetate and filtered through a pad of silica gel. The filtrate was concentrated under reduced pressure to give an orange solid. This solid was recrystallized from hexane-ethyl acetate to give the title compound (0.26 g, 59%) as a light yellow solid.

Workup

  1. temperatureto warm to room temperature
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in pyridine (10 mL)
  4. stirringthe mixture was stirred at room temperature for 16 h
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. customthe resulting residue was partitioned between ethyl acetate and 10% NaHCO3 solution
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe resulting solid was dissolved in ethyl acetate
  12. filtrationfiltered through a pad of silica gel
  13. concentrationThe filtrate was concentrated under reduced pressure
  14. customto give an orange solid
  15. customThis solid was recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-b7a6d5ebbfd3451c9893fc2e4cf015c2
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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