Methyl vinyl ketone → 1-[3-Fluoro-4-(methylthio)phenyl]pentane-1,4-dione

HRID 1597491Notes

Reaction equation

HRID 1597491 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[S:10][CH3:11])[CH:5]=[O:6].[CH:12]([C:14]([CH3:16])=[O:15])=[CH2:13].CCN(CC)CC>C(O)C.[Cl-].C([N+]1C(C)=C(CCO)SC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:5](=[O:6])[CH2:13][CH2:12][C:14](=[O:15])[CH3:16])[CH:7]=[CH:8][C:9]=1[S:10][CH3:11]

Participants

6

Reactant 3

HCID 6570Methyl vinyl ketoneHCID 8471TriethylamineHCID 112752573-Fluoro-4-(methylthio)benzaldehyde

Product 1

HCID 223169141-[3-Fluoro-4-(methylthio)phenyl]pentane-1,4-dioneYield 73%

Reagents, catalysts & solvents 2

HCID 28333523-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chlorideCatalystHCID 702EthanolSolvent

Procedure

To a stirred solution of 3-fluoro-4-(methylthio)benzaldehyde (3.04 g, 17.9 mmol) in ethanol (12 mL) was added methyl vinyl ketone (1.3 mL, 15.5 mmol), 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride (0.84 g, 3.1 mmol), and Et3N (4.32 mL, 31 mmol) at room temperature. After stirring for 2 hours, volatiles were removed by evaporation. The residue was taken up with ethyl acetate (200 mL), and washed with water (120 mL), dil. aqueous HCl (120 mL), water (120 mL), brine (120 mL), dried over MgSO4, and concentrated in vacuo. The resulting crude residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1/2) to provide 1-[3-fluoro-4-(methylthio)phenyl]pentane-1,4-dione (2.7 g, 73% yield). To a stirred suspension of 1-[3-fluoro-4-(methylthio)phenyl]pentane-1,4-dione (2.7 g, 11.25 mmol) in methanol (50 mL) was added Oxone (14.14 g, 23 mmol) in water (50 mL) at room temperature. After stirring for 5 hours, the mixture was diluted with water. The whole was extracted with CH2Cl2 (50 mL×4), the combined organic layer washed with brine, dried over MgSO4, and evaporated in vacuo to give the subtitle compound (2.8 g, 66% yield).

Workup

  1. customvolatiles were removed by evaporation
  2. washwashed with water (120 mL), dil. aqueous HCl (120 mL), water (120 mL), brine (120 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting crude residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1/2)

Sources & evidence

ORD record
ord-7db284ec79924ce5b76a0b2747c9b5b8
Source dataset
uspto-grants-2001_09
Patent number
US06294558B1

Reaction notes

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