Hydrochloric Acid → 2-(3-Oxo-cyclohexyl)-malonic acid dibenzyl ester

HRID 352213Notes

Reaction equation

HRID 352213 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[Na].[C:8]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:13])[CH2:9][C:10]([O-:12])=[O:11].[H-].[Na+].[C:24]1(=[O:30])[CH2:29][CH2:28][CH2:27][CH:26]=[CH:25]1.Cl>C1COCC1>[CH2:15]([O:14][C:8](=[O:13])[CH:9]([CH:26]1[CH2:27][CH2:28][CH2:29][C:24](=[O:30])[CH2:25]1)[C:10]([O:12][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:11])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 135942-Cyclohexen-1-oneHCID 24758Sodium hydrideHCID 5360545SodiumHCID 21226445Aluminium lithium hydrideHCID 22247814Benzyl malonate

Product 1

HCID 66361702-(3-Oxo-cyclohexyl)-malonic acid dibenzyl esterYield 141.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of LiAlH4 (6 mL, 6 mmol) under N2 at 0° C. was added a solution of (S)-1,1′-binaphthol (3.43 g, 12 mmol) in THF (48 mL) and stirred for 30 min. The reaction was warmed to RT. To this was added a solution of sodium salt benzyl malonate in THF which was prepared by reacting benzyl malonate (14.99 mL, 60 mmol), NaH (60% by wt., 0.216 g, 5.4 mmol), and THF (60 mL) until all bubbling ceased. Next, cyclohexenone (5.82 mL, 60 mmol) and dibenzlmalonate (1.35 mL, 5.4 mmol) were added and the reaction mixture was stirred overnight. 1.0 N HCl was added and extracted with EtOAc (3×). The combined EtOAc layers were washed (brine), dried (MgSO4), filtered, and concentrated. Flash chromatography (silica gel, acetone/hexanes gradient) gave the title compound (16.17 g, 71%). Mass Spectrum (FIA) (m/z) 381.3 [M+1].

Workup

  1. customwas prepared
  2. stirringthe reaction mixture was stirred overnight
  3. extractionextracted with EtOAc (3×)
  4. washThe combined EtOAc layers were washed (brine)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f2db9d22d5154db5a0d3ad6dc5f475cf
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Reaction notes

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