Tert-butyl 3-oxopyrrolidine-1-carboxylate → HCID 69694946, compound

HRID 2181711Notes

Reaction equation

HRID 2181711 reaction equation
[CH2:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][C:7]=2C1CCCNC1)[CH3:2].C([Li])CCC.[C:24]([O:28][C:29]([N:31]1[CH2:35][CH2:34][C:33](=[O:36])[CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>O1CCCC1>[C:24]([O:28][C:29]([N:31]1[CH2:35][CH2:34][C:33]([C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:6]=2[N:5]=[CH:4][C:3]([CH2:1][CH3:2])=[CH:12]3)([OH:36])[CH2:32]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

5

Reactant 3

HCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 10037308HCID 10037308, compoundHCID 178418339Butyllithium

Product 1

HCID 69694946HCID 69694946, compoundYield 11.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-77 °C

Procedure

To a well-stirred solution of the title compound of Example 1, Step 1 (2.10 g, 8.9 mmol) in 30 ml of anhydrous tetrahydrofuran chilled to and maintained at −77° C., a 2.5 M solution of n-butyl lithium in hexanes (3.60 ml, 8.9 mmol; Aldrich Chemical Co.) is added dropwise over a 10 minute period. The reaction was stirred at −77° C. for 15 minutes before adding a solution of 3-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (1.65 g, 8.9 mmol) in anhydrous tetrahydrofuran (10 ml). The reaction mixture was allowed to warm to ambient temperature and stir at that temperature for 3 hours before quenching by cautious dropwise addition (with cooling) of saturated aqueous sodium bicarbonate (50 ml total). The resulting mixture was thoroughly extracted with three 20 ml of ethyl acetate. The combined organic extracts were, in turn, extracted with an equal volume portion of brine, dried (anhydrous sodium sulfate) and, finally, concentrated in vacuo, yielding a viscous syrup. Flash chromatography of the entire sample (silica gel, 47-61 micron mesh; elution with methylene chloride/methanol=98:2 in volume) afforded the title compound (352 mg, 11.5% yield) as a viscous yellow oil.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstir at that temperature for 3 hours
  3. custombefore quenching by cautious dropwise addition (with cooling) of saturated aqueous sodium bicarbonate (50 ml total)
  4. extractionThe resulting mixture was thoroughly extracted with three 20 ml of ethyl acetate
  5. extractionextracted with an equal volume portion of brine
  6. dry with materialdried (anhydrous sodium sulfate)
  7. concentrationfinally, concentrated in vacuo
  8. customyielding a viscous syrup
  9. washFlash chromatography of the entire sample (silica gel, 47-61 micron mesh; elution with methylene chloride/methanol=98:2 in volume)

Sources & evidence

ORD record
ord-045ca64987394a8da2ac4d9fe675d797
Source dataset
uspto-grants-2005_05
Patent number
US06894062B1

Reaction notes

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