Tetrahydrofuran → (+/-)-Methyl {4-[2,4-bis(methoxymethoxy)phenyl]cyclohexylidene}acetate

HRID 585664Notes

Reaction equation

HRID 585664 reaction equation
[H-].[Na+].C[C:4](P(OC)(O)=O)([C:6]([O-:8])=[O:7])[CH3:5].[CH3:14][O:15][CH2:16][O:17][C:18]1[CH:23]=[C:22]([O:24][CH2:25][O:26][CH3:27])[CH:21]=[CH:20][C:19]=1[CH:28]1[CH2:33][CH2:32]C(=O)[CH2:30][CH2:29]1.O1CCC[CH2:36]1>>[CH3:14][O:15][CH2:16][O:17][C:18]1[CH:23]=[C:22]([O:24][CH2:25][O:26][CH3:27])[CH:21]=[CH:20][C:19]=1[CH:28]1[CH2:33][CH2:32][C:5](=[CH:4][C:6]([O:8][CH3:36])=[O:7])[CH2:30][CH2:29]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 121351704-[2,4-Bis(methoxymethoxy)phenyl]cyclohexanoneHCID 53413272Trimethylphosphonoacetate

Product 1

HCID 91541557(+/-)-Methyl {4-[2,4-bis(methoxymethoxy)phenyl]cyclohexylidene}acetateYield 95%

Conditions

Temperature
0 °C

Procedure

A round bottomed flask equipped with magnetic stirrer was loaded with sodium hydride (0.20 g, 5.10 mmol, 60% dispersion in mineral oil) which was washed with petroleum ether (4×20 ml). The excess petroleum ether was removed under reduced pressure. Anhydrous tetrahydrofuran (120 ml) was added and the stirred solution was cooled to 0° C. Trimethylphosphonoacetate (756 μl, 5.10 mmol) was added dropwise via syringe and the stirred mixture was allowed to warm to room temperature over 1 hr. The mixture was cooled to 0° C. prior to the addition of 4-[2,4-bis(methoxymethoxy)phenyl]cyclohexanone (1.00 g, 3.40 mmol) as a solution in tetrahydrofuran (30 ml). The pale yellow mixture was heated to reflux temperature for 0.75 hr, then cooled to room temperature and partitioned between ethyl acetate (100 ml) and saturated aqueous ammonium chloride solution (30 ml). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×30 ml). The combined organic layers were washed with brine (30 ml), dried over magnesium sulfate, filtered and concentrated in vacuo, affording a yellow oil. Purification via flash column chromatography (SiO2, ethyl acetate/petroleum ether, 1:2, v/v) furnished the title compound as a yellow oil (1.13 g, 95%). δH(CD3OD) 1.53-1.70 (2H, m), 2.00-2.13 (4H, m), 2.45 (2H, m), 3.26 (1H, m), 3.48 (3H, s), 3.53 (3H, s), 3.71 (3H, s), 5.17 (2H, s), 5.24 (2H, s), 5.73 (1H, s), 6.67 and 6.68 (1H, d), 6.83 (1H, d), 7.08 (1H, d).

Workup

  1. customA round bottomed flask equipped with magnetic stirrer
  2. washwas washed with petroleum ether (4×20 ml)
  3. customThe excess petroleum ether was removed under reduced pressure
  4. additionAnhydrous tetrahydrofuran (120 ml) was added
  5. temperatureto warm to room temperature over 1 hr
  6. temperatureThe mixture was cooled to 0° C.
  7. temperatureThe pale yellow mixture was heated
  8. temperatureto reflux temperature for 0.75 hr
  9. temperaturecooled to room temperature
  10. custompartitioned between ethyl acetate (100 ml) and saturated aqueous ammonium chloride solution (30 ml)
  11. customThe layers were separated
  12. extractionthe aqueous layer was extracted with ethyl acetate (3×30 ml)
  13. washThe combined organic layers were washed with brine (30 ml)
  14. dry with materialdried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customaffording a yellow oil
  18. customPurification via flash column chromatography (SiO2, ethyl acetate/petroleum ether, 1:2, v/v)

Sources & evidence

ORD record
ord-fccaaf94c01d4575b4134c88979dfc12
Source dataset
uspto-grants-2005_08
Patent number
US06933319B2

Reaction notes

Loading…