Ethyl Acetate → HCID 59464241, compound

HRID 1713867Notes

Reaction equation

HRID 1713867 reaction equation
[H-].[Na+].[CH3:3]N(C)C(=N)N(C)C.O[C:12]1[CH:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)=[CH:14][CH:13]=1.[Cl-].[NH4+].[CH3:27][CH2:28][O:29][C:30]([CH3:32])=[O:31]>C1COCC1>[OH:24][C:21]1[CH:22]=[CH:23][C:18]([CH:15]2[CH2:16][CH2:17][C:12](=[C:32]([CH3:3])[C:30]([O:29][CH2:28][CH3:27])=[O:31])[CH2:13][CH2:14]2)=[CH:19][CH:20]=1

Participants

7

Reactant 5

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 664601,1,3,3-TetramethylguanidineHCID 45989164-(4'-Hydroxyphenyl)cyclohexanone

Product 1

HCID 59464241HCID 59464241, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
11 °C

Procedure

A solution of triethylphosphonopropionate (12.5 g, 52.6 mmol) in THF (10 mL) was added in one portion to a stirred mixture of sodium hydride (60% in mineral oil, 2.3 g, 57.6 mmol) in THF (75 mL) and the reaction mixture was stirred at 11° C. under an argon atmosphere for 1 h. In a separate flask tetramethylguanidine (6.61 g, 57.4 mmol) was added in one portion to a solution of 4-(4-hydroxyphenyl)cyclohexanone (9.1 g, 47.8 mmol) in THF (40 mL) at 10° C. under an argon atmosphere and the stirred mixture was warmed to room temperature over 1 h. This mixture was added in one portion to the triethylphosphonopropionate mixture at 10° C. and the combined reaction mixture was warmed to ambient temperature and stirred for 18 h under an argon atmosphere. A saturated aqueous solution of ammonium chloride (75 mL) and EtOAc (100 mL) were added. The layers were separated and the aqueous layer was extracted with EtOAc (100 mL). The combined organic layers were dried and concentrated in vacuo to leave a residue. The residue was triturated with a mixture of ether and isohexane (2:1), filtered and the filtrate was concentrated in vacuo to give the title compound (6.9 g, 53%) as a solid; 1H NMR δ 1.21 (3H, t), 1.33-1.5 (2H, m), 1.78-2.1 (4H, m), 1.84 (3H, s), 2.6-2.78 (2H, m), 2.99-3.09 (1H, m), 4.12 (2H, q), 6.67 (2H, d), 7.02 92H, d), 9.08 (1H, s); MS m/e MH+ 275.

Workup

  1. temperaturethe stirred mixture was warmed to room temperature over 1 h
  2. customthe combined reaction mixture
  3. temperaturewas warmed to ambient temperature
  4. stirringstirred for 18 h under an argon atmosphere
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (100 mL)
  7. customThe combined organic layers were dried
  8. concentrationconcentrated in vacuo
  9. customto leave a residue
  10. customThe residue was triturated with a mixture of ether and isohexane (2:1)
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-12754e454d764ffa86d963799acd0305
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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