Ethyl Acetate → HCID 67360599, compound

HRID 1667197Notes

Reaction equation

HRID 1667197 reaction equation
[C:1]1([C:7]2([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC([O-])(C)C.[K+].Br[CH2:26][CH2:27][CH2:28][C:29]([O:31]C(C)(C)C)=[O:30].C(OCC)(=O)C>O1CCCC1>[O:12]=[C:8]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:11][CH2:10][N:9]1[CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 2382533,3-Diphenyl-2-pyrrolidinoneHCID 2757253tert-Butyl 4-bromobutanoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 67360599HCID 67360599, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

To a suspension of 3,3-diphenylpyrrolidin-2-one (2.00 g, 8.43 mmol; Example 1A) in tetrahydrofuran (10 mL) was added potassium 2-methylpropan-2-olate (9.27 mL, 9.27 mmol). After stirring for 30 minutes, the reaction was a suspension so the reaction was heated to 40° C. The reaction was cooled to ambient temperature, and then tert-butyl 4-bromobutanoate (2.068 g, 9.27 mmol) as a solution in tetrahydrofuran (3 mL) was added. The reaction was stirred for 3 hours, then poured into ethyl acetate/1 N HCl (1:1, 300 mL). The organic layer was separated, washed with brine (100 mL), dried over magnesium sulfate and concentrated. The residue was loaded onto a GraceResolv™ 40 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 30 minutes. The product was dissolved in 5 mL of dichloromethane then 5 mL of trifluoroacetic acid was added. After stirring for 3 hours, the reaction was concentrated to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.36-7.22 (m, 10H), 3.45 (m, 4H), 2.79 (t, J=6.5, 2H), 2.31 (t, J=7.1, 2H), 1.89 (p, J=7.0, 2H); MS (ESI+) m/z 324.0 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. stirringThe reaction was stirred for 3 hours
  3. customThe organic layer was separated
  4. washwashed with brine (100 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 30 minutes
  8. dissolutionThe product was dissolved in 5 mL of dichloromethane
  9. addition5 mL of trifluoroacetic acid was added
  10. stirringAfter stirring for 3 hours
  11. concentrationthe reaction was concentrated

Sources & evidence

ORD record
ord-1d8f836c451a4a54836b0ce7f5f24184
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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