Propionic Acid → beta-Oxo-delta-phenyl-benzene pentanoic acid ethyl ester

HRID 1198033Notes

Reaction equation

HRID 1198033 reaction equation
[C:1]1([CH:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:8][C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N1C=CN=C1)(N1[CH:24]=[CH:23]N=C1)=O.[Cl-].[Mg+2].[Cl-].C(O)(=O)[CH2:34][C:35]([OH:37])=[O:36].C([K])C.C(N(CC)CC)C.C(O)(=O)CC.C([O-])(=O)CC([O-])=O>C1COCC1.C(#N)C>[CH2:23]([O:37][C:35](=[O:36])[CH2:34][C:9](=[O:11])[CH2:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:24]

Participants

10

Reactant 7

HCID 1032Propionic AcidHCID 8471TriethylamineHCID 9084Malonate IonHCID 64798Diphenylpropionic acid2×HCID 682631,1'-CarbonyldiimidazoleHCID 5360315Magnesium ChlorideHCID 178461627HCID 178461627, compound

Product 1

HCID 15105219beta-Oxo-delta-phenyl-benzene pentanoic acid ethyl esterYield 51%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution (0° C.) of 3,3-diphenylpropionic acid (50.0 g, 0.220 mol) in 300 mL THF, 1,1'-carbonyldiimidazole (43.0 g, 0.265 mol) was added portionwise (exotherm to 10° C.) and stirred at 0° C. for 3 hours. After 3 hours, in a separate flask (equipped with an overhead stirrer), magnesium chloride (40.0 g, 0.418 mol) was added to a cooled solution (0° C.) of ethyl potassium malonate (60.0 g, 0.352 mol) in 400 mL acetonitrile (exotherm to 30° C.). Triethylamine (48.9 g, 0.484 mol) was then added and this mixture and the 3,3-diphenylpropionic acid mixture were separately allowed to gradually warm to room temperature and stir for 4 hours. The propionic acid mixture was then added dropwise to the malonate mixture (exotherm to 30° C.) and this reaction mixture was stirred at room temperature for 16 hours. This pale yellow heterogeneous reaction mixture was then carefully quenched with a solution of 200 g sodium bisulfate in 700 mL water. Ethyl acetate (3L) was then added to the yellow homogeneous solution, the layers were separated, and the organic layer was washed with 1L 5% NAOH solution and 1L saturated NaCl solution. The organic layer was then diluted with 1.5L hexane, dried (MgSO4), and concentrated in vacuo (30° C.) to give a yellow oil. Purification by flash chromatography (silica gel, 15% EtOAc/hexane) yielded 33.2 g (0.112 mol, 51%) of the desired product.

Workup

  1. waitAfter 3 hours
  2. temperatureto gradually warm to room temperature
  3. stirringstir for 4 hours
  4. stirringthis reaction mixture was stirred at room temperature for 16 hours
  5. customThis pale yellow heterogeneous reaction mixture was then carefully quenched with a solution of 200 g sodium bisulfate in 700 mL water
  6. additionEthyl acetate (3L) was then added to the yellow homogeneous solution
  7. customthe layers were separated
  8. washthe organic layer was washed with 1L 5% NAOH solution and 1L saturated NaCl solution
  9. additionThe organic layer was then diluted with 1.5L hexane
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo (30° C.)
  12. customto give a yellow oil
  13. customPurification by flash chromatography (silica gel, 15% EtOAc/hexane)

Sources & evidence

ORD record
ord-cca28913dc0b4aef9f81b1242ce45254
Source dataset
uspto-grants-1994_01
Patent number
US05278326

Reaction notes

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