(3-Bromopropyl)benzene → Methyl 2-oxo-3-(3-phenylpropyl-1-yl)cyclopentanecarboxylate

HRID 1107126Notes

Reaction equation

HRID 1107126 reaction equation
[H-].[Na+].[O:3]=[C:4]1[CH2:8][CH2:7][CH2:6][CH:5]1[C:9]([O:11][CH3:12])=[O:10].C([Li])CCC.Br[CH2:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1.O>[O:3]=[C:4]1[C:8](=[CH:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:7][CH2:6][CH:5]1[C:9]([O:11][CH3:12])=[O:10]

Participants

7

Reactant 4

HCID 12503(3-Bromopropyl)benzeneHCID 24758Sodium hydrideHCID 66328Cyclopentanecarboxylic acid, 2-oxo-, methyl esterHCID 178418339Butyllithium

Product 1

HCID 69907747Methyl 2-oxo-3-(3-phenylpropyl-1-yl)cyclopentanecarboxylateYield 13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 60% NaH (1.2 g, 30 mmol) in anhydrous THF (30 mL) in an ice bath is added a solution of methyl 2-oxocyclopentanecarboxylate (4.26 g, 30 mmol) in 10 mL of THF dropwise over 5 minutes. The mixture is stirred at room temperature for 20 minutes. The mixture is cooled to -25° C. and 2.5 M n-butyllithium is added over 5 minutes (12 mL, 30 mmol). After stirring for 5 minutes, 1-bromo-3-phenylpropane (4.6 mL, 30 mmol) is added. The mixture is stirred at room temperature for 3 hours. The mixture is poured into water and is extracted with ether. The organic layer is washed with water and is dried over MgSO4. The solvent is removed in vacuo and the residue is chromatographed on silica gel (6:1 hexane:ethyl acetate) to afford methyl 2-oxo-3-(3-phenylpropyl-1-yl)cyclopentanecarboxylate (1 g, 13%): 1H-NMR (300 MHz, CDCl3) δ (TMS) 1.22-1.50 (m, 2H), 1.62-1.90 (m, 4H), 2.12-2.38 (m, 4H), 2.58-2.69 (m, 2H), 3.75 (s, 3H), 7.10-7.32 (m, 5H); MS (EI) m/e 260 (M+).

Workup

  1. temperatureThe mixture is cooled to -25° C.
  2. stirringAfter stirring for 5 minutes
  3. stirringThe mixture is stirred at room temperature for 3 hours
  4. extractionis extracted with ether
  5. washThe organic layer is washed with water
  6. dry with materialis dried over MgSO4
  7. customThe solvent is removed in vacuo
  8. customthe residue is chromatographed on silica gel (6:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-9446325064164e7ca0e6dd5c33cf76ed
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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