Sodium Hydroxide → 3-(2-Ethoxy-2-oxoethyl)cyclopentanecarboxylicacid

HRID 505271Notes

Reaction equation

HRID 505271 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1.[OH-].[Na+].CC[O-].[Na+].[CH:20]([O-:22])=[O:21].[NH4+]>CCO.[Pd].CC(O)=O>[CH2:12]([O:11][C:9](=[O:10])[CH2:8][CH:5]1[CH2:6][CH2:7][CH:2]([C:20]([OH:22])=[O:21])[CH2:3][CH2:4]1)[CH3:13]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 2723922Sodium ethoxideHCID 2723923Ammonium formateHCID 12666966Ethyl 2-(4-oxocyclohexyl)acetate

Product 1

HCID 187838263-(2-Ethoxy-2-oxoethyl)cyclopentanecarboxylicacid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolvent2×

Procedure

A three liter round bottom flask was charged with ethyl (4-oxocyclohexyl)acetate (100 g, 0.588 mol) and ethanol (400 mL). Sodium hydroxide (25.8 g, 0.645 mol) was added, and the reaction was stirred at room temperature for 1 hour. Next, triethyl phosphonoacetate (128 mL, 0.645 mol) was added, and the reaction was then cooled to 0° C. A solution of NaOEt in EtOH (21% solution, 242 mL) was added dropwise to the reaction over 1 hour. The reaction was warmed to room temperature and stirred for 1 hour. HOAc (84 mL) was added, followed by ammonium formate (74 g) and 5% Pd/C (10 g). The reaction was heated to 60° C. for 6 hours and then cooled to room temperature. The solids were filtered off and the filtrate was concentrated. The residue was taken up in EtOAc (2 L) and washed with 1N HCl (2×500 mL), H2O (500 mL), and brine (500 mL). The organic layer was concentrated to an oil and azeotroped with toluene (2 L). The residue was purified by flash chromatography on silica gel (0 to 50% EtOAc/Hexanes containing 1% HOAc). This afforded 4-(2-ethoxy-2-oxoethyl)cyclohexanecarboxylic acid as a mixture of cis and trans isomers.

Workup

  1. temperaturethe reaction was then cooled to 0° C
  2. temperatureThe reaction was warmed to room temperature
  3. stirringstirred for 1 hour
  4. temperatureThe reaction was heated to 60° C. for 6 hours
  5. temperaturecooled to room temperature
  6. filtrationThe solids were filtered off
  7. concentrationthe filtrate was concentrated
  8. washwashed with 1N HCl (2×500 mL), H2O (500 mL), and brine (500 mL)
  9. concentrationThe organic layer was concentrated to an oil
  10. customazeotroped with toluene (2 L)
  11. customThe residue was purified by flash chromatography on silica gel (0 to 50% EtOAc/Hexanes containing 1% HOAc)
  12. additionThis afforded 4-(2-ethoxy-2-oxoethyl)cyclohexanecarboxylic acid as a mixture of cis and trans isomers

Sources & evidence

ORD record
ord-b396f8a198fc449e93d3f671556585c8
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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