反応 #433495

反応方程式

potassium tert-butoxide

ethyl 3-methyl-4-oxobutenoate

3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonic acid diethyl ester

3-Methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonic Acid, Diethyl Ester

dimethyl sulfoxide

→

ethyl retinoate

収率 61.0%

溶媒

pentane

tetrahydrofuran

反応条件

後処理

1. 1
   その他an alternate synthesis
2. 2
   workup.WAITat room temperature for 6 hours
3. 3
   洗浄ether and subsequent washing of the organic layer with 30 mL portions of 10% aqueous sodium chloride (3×30 mL)
4. 4
   乾燥The organic layer was then dried over anhydrous magnesium sulfate
5. 5
   ろ過filtered
6. 6
   その他Removal of the volatile organic solvents
7. 7
   その他by evaporation at reduced pressure
8. 8
   ろ過followed by filtration through a small column of silica gel (15 mL, 60-200 mesh, elution with 75 mL of hexane--4% ether)
9. 9
   その他to remove

実験手順

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, N.Y. 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-oxobutenoate and 3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonic acid diisopropyl ester (produced in accordance with Example XI).

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