Ethyl 4-thiomethylbenzoylformate → (E)-4-Cyclohexyl-2-(4-methylsulfanyl-phenyl)-but-2-enoic acid ethyl ester

HRID 2103585Notes

Reaction equation

HRID 2103585 reaction equation
[K].CC(C)([O-])C.[I-].[CH:8]1([CH2:14][CH2:15][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.[CH2:35]([O:37][C:38](=[O:49])[C:39]([C:41]1[CH:46]=[CH:45][C:44]([S:47][CH3:48])=[CH:43][CH:42]=1)=O)[CH3:36]>C1COCC1>[CH2:35]([O:37][C:38](=[O:49])/[C:39](/[C:41]1[CH:46]=[CH:45][C:44]([S:47][CH3:48])=[CH:43][CH:42]=1)=[CH:15]/[CH2:14][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[CH3:36]

Participants

5

Reactant 3

HCID 2758911Ethyl 4-thiomethylbenzoylformateHCID 50987170Potassium tertbutoxideHCID 85983208(2-Cyclohexyl-ethyl)-triphenyl-phosphonium iodide

Product 1

HCID 67084509(E)-4-Cyclohexyl-2-(4-methylsulfanyl-phenyl)-but-2-enoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add potassium-tert.-butoxide (4.3 mL, 1.0 M in THF, 4.3 mmol) to a suspension of (2-cyclohexyl-ethyl)-triphenyl-phosphonium iodide (2.15 g, 4.3 mmol) at room temperature and stir the reaction mixture for 1 h. Dissolve (4-methylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (prepared as described by I. T. Barnish et. al. J. Med. Chem. 1981, 24, 399-404) in THF and add the resulting solution to the reaction mixture. Stir at room temperature over night. Evaporate the solvent and add 15 mL hexane to the remaining solid. Stir at 40° C. for 30 minutes, filter and concentrate the filtrate under vacuum to afford 1.3 g raw material as a yellow oil. Further purify this material via silica gel chromatography, eluting with a gradient from 98:2 to 90:10 hexane:ethyl acetate to afford a colorless oil (379 mg).

Workup

  1. stirringStir at room temperature over night
  2. customEvaporate the solvent
  3. additionadd 15 mL hexane to the remaining solid
  4. stirringStir at 40° C. for 30 minutes
  5. filtrationfilter
  6. concentrationconcentrate the filtrate under vacuum
  7. customto afford 1.3 g raw material as a yellow oil
  8. customFurther purify this material via silica gel chromatography
  9. washeluting with a gradient from 98:2 to 90:10 hexane

Sources & evidence

ORD record
ord-24febf02ea824c0e81e70dd5dfe08fc3
Source dataset
uspto-grants-2009_08
Patent number
US07576108B2

Reaction notes

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