Dimethyl Sulfoxide → ethyl (2Z,4E,6Z,8Z)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoate

HRID 2073407Notes

Reaction equation

HRID 2073407 reaction equation
[CH3:1][C:2]([CH:9]=O)=[CH:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:11][C:12]([CH:23]=[CH:24][C:25]1[C:30]([CH3:32])([CH3:31])[CH2:29][CH2:28][CH2:27][C:26]=1[CH3:33])=[CH:13][CH2:14]P(=O)(OCC)OCC.CS(C)=O.CC(C)([O-])C.[K+]>O1CCCC1.CCCCC>[CH3:8][CH2:7][O:6][C:4](/[CH:3]=[C:2](\[CH:9]=[CH:14]\[CH:13]=[C:12](/[CH:23]=[CH:24]\[C:25]1[C:30]([CH3:32])([CH3:31])[CH2:29][CH2:28][CH2:27][C:26]=1[CH3:33])\[CH3:11])/[CH3:1])=[O:5]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 3016304Ethyl 3-methyl-4-oxocrotonateHCID 23665647Potassium tert-butoxideHCID 541752833-Methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonic Acid, Diethyl Ester

Product 1

HCID 6439682ethyl (2Z,4E,6Z,8Z)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoateYield 61%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 57 mg (0.40 mmole) of ethyl 3-methyl-4-oxobutenoate [prepared according to a procedure described by R. W. Curley, Jr., et al., J. Org. Chem., 51, 256 (1986); an alternate synthesis has been described by A. Guingant, et al., J. Org. Chem., 52, 4788 (1987); the compound is commercially available from Fluka Chemical Corp., Ron Kon Koma, New York 11779.] and 132 mg (0.388 mmole) of 3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonic acid diethyl ester (produced in accordance with Example X) in 3.5 mL of 6:1 (v/v) anhydrous tetrahydrofuran:dimethyl sulfoxide, protected from atmospheric moisture and maintained at a temperature of approximately 5° C. by use of an ice water bath, was added 43 mg (0.38 mmole) of potassium tert-butoxide. This mixture was subsequently stirred in the cold for 10 minutes and then at room temperature for 6 hours. The product was isolated by dilution of the mixture with 30 mL of 1:1 (v/v) pentane:ether and subsequent washing of the organic layer with 30 mL portions of 10% aqueous sodium chloride (3×30 mL). The organic layer was then dried over anhydrous magnesium sulfate and filtered. Removal of the volatile organic solvents by evaporation at reduced pressure, followed by filtration through a small column of silica gel (15 mL, 60-200 mesh, elution with 75 mL of hexane-4% ether) to remove any unreacted starting materials, afforded 76 mg (61% yield) of ethyl retinoate shown by high-field (300 MHz) NMR analysis to be predominantly the all trans stereoisomer. The product was characterized by three broad singlets of equal intensity at δ 2.37, 2.02, and 1.73 (3 vinyl methyls). For tables listing spectroscopic properties of retinoids, see: R. S. H. Liu, et al. Tetrahedron, 40, 1931-1969 (1984). Ethyl retinoate was also prepared in a similar manner from ethyl 3-methyl-4-oxo-butenoate and 3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonic acid diisopropyl ester (produced in accordance with Example XI).

Workup

  1. customan alternate synthesis
  2. waitat room temperature for 6 hours
  3. washether and subsequent washing of the organic layer with 30 mL portions of 10% aqueous sodium chloride (3×30 mL)
  4. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customRemoval of the volatile organic solvents
  7. customby evaporation at reduced pressure
  8. filtrationfollowed by filtration through a small column of silica gel (15 mL, 60-200 mesh, elution with 75 mL of hexane-4% ether)
  9. customto remove

Sources & evidence

ORD record
ord-4e045470782444d08c1032c368dbc5e4
Source dataset
uspto-grants-1990_04
Patent number
US04916250

Reaction notes

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