Cyclopentanone → 4-{1-Ethyl-1-[4-(1-hydroxy-cyclopentylethynyl)-3-methyl-phenyl]-propyl}-2-methyl-benzoic acid methyl ester

HRID 736515Notes

Reaction equation

HRID 736515 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH2:22][CH3:23])([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[CH:20])=[C:15]([CH3:21])[CH:14]=2)[CH2:11][CH3:12])=[CH:6][C:5]=1[CH3:24].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:36]1(=[O:41])[CH2:40][CH2:39][CH2:38][CH2:37]1>C1COCC1>[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH2:11][CH3:12])([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:36]3([OH:41])[CH2:40][CH2:39][CH2:38][CH2:37]3)=[C:15]([CH3:21])[CH:14]=2)[CH2:22][CH3:23])=[CH:6][C:5]=1[CH3:24]

Participants

5

Reactant 3

HCID 8452CyclopentanoneHCID 2733832Lithium HexamethyldisilazideHCID 57849361HCID 57849361, compound

Product 1

HCID 578493504-{1-Ethyl-1-[4-(1-hydroxy-cyclopentylethynyl)-3-methyl-phenyl]-propyl}-2-methyl-benzoic acid methyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a −78 C solution of 4-[1-Ethyl-1-(4-ethynyl-3-methyl-phenyl)-propyl]-2-methyl-benzoic acid methyl ester (2.50 g, 7.47 mmol) in THF (80 ml) is added lithium hexamethyldisilazide (8.22 ml, 8.22 mmol, 1.0 M in THF) and stirred at −78 C for 30 min. Cyclopentanone (730 μL, 8.22 mmol) is added and the reaction mixture warmed to room temperature. The reaction is quenched with saturated aqueous NH4Cl (30 ml) and concentrated. The residue is partitioned between EtOAc (300 ml) and 1.0N HCl (50 ml). The aqueous layer is extracted with EtOAc (100 ml). The combined organic layer are washed with water (50 ml), brine (50 ml), dried (MgSO4), concentrated and chromatographed (120 g SiO2, 5% EtOAc/Hexanes) to yield the title compound (2.45 g, 79%).

Workup

  1. customThe reaction is quenched with saturated aqueous NH4Cl (30 ml)
  2. concentrationconcentrated
  3. customThe residue is partitioned between EtOAc (300 ml) and 1.0N HCl (50 ml)
  4. extractionThe aqueous layer is extracted with EtOAc (100 ml)
  5. washThe combined organic layer are washed with water (50 ml), brine (50 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customchromatographed (120 g SiO2, 5% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-3eedbf348981468fa24d54f2e3ca51d3
Source dataset
uspto-grants-2009_09
Patent number
US07595345B2

Reaction notes

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