Potassium Hydroxide → Ethyl 2-(4-benzyloxybenzyl)-5-phenylvalerate

HRID 1859944Notes

Reaction equation

HRID 1859944 reaction equation
[OH-].[K+].[CH2:3]([O:10][C:11]1[CH:37]=[CH:36][C:14]([CH2:15][C:16]([CH2:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)(C(OCC)=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>COCCO.O>[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:15][CH:16]([CH2:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:36][CH:37]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 18625695Diethyl 2-(4-benzyloxybenzyl)-2-(3-phenylpropyl)malonate

Product 1

HCID 18625892Ethyl 2-(4-benzyloxybenzyl)-5-phenylvalerateYield 100.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
130 °C

Procedure

Potassium hydroxide (2.00 g) was added to a solution of diethyl 2-(4-benzyloxybenzyl)-2-(3-phenylpropyl)malonate (3.91 g) in a mixture of 2-methoxyethanol (30 ml) and water (3 ml). The mixture was stirred at 130° C. in an oil bath for 1.5 hours. At the end of this time the reaction mixture was partitioned between ethyl acetate and water and the mixture was acidified with aqueous hydrogen chloride solution (6N). The ethyl acetate layer was separated and washed with aqueous sodium chloride solution and dried over anhydrous magnesium sulfate and concentrated. A solution of the residual syrup in xylene (20 ml) was stirred for 1 hour and then concentrated. Concentrated sulfuric acid (1 ml) was added to a solution of the syrup residue of 2-(4-benzyloxybenzyl)-5-phenylvaleric acid in ethanol (40 ml). The mixture was stirred at 80° C. for 3 hours and allowed to stand at ambient temperature for 16 hours. At the end of this time the reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The ethyl acetate layer was separated and dried over anhydrous magnesium sulfate and concentrated to dryness to afford the desired compound (3.32 g) as a syrup.

Workup

  1. customAt the end of this time the reaction mixture was partitioned between ethyl acetate and water
  2. customThe ethyl acetate layer was separated
  3. washwashed with aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. stirringA solution of the residual syrup in xylene (20 ml) was stirred for 1 hour
  7. concentrationconcentrated
  8. additionConcentrated sulfuric acid (1 ml) was added to a solution of the syrup residue of 2-(4-benzyloxybenzyl)-5-phenylvaleric acid in ethanol (40 ml)
  9. stirringThe mixture was stirred at 80° C. for 3 hours
  10. waitto stand at ambient temperature for 16 hours
  11. concentrationAt the end of this time the reaction mixture was concentrated
  12. customthe residue was partitioned between ethyl acetate and water
  13. customThe ethyl acetate layer was separated
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-aed41ea71891457f9c497e20548849f2
Source dataset
uspto-grants-2003_03
Patent number
US06528525B1

Reaction notes

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