5-[(4-Chlorophenyl){6-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}methyl]-2,2-dimethyl-1,3-dioxane-4,6-dione → Ethyl 3-(4-chlorophenyl)-3-{6-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}propanoate

HRID 561406Notes

Reaction equation

HRID 561406 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[C:27]3[C:22](=[C:23]([CH2:29][S:30][CH3:31])[C:24]([F:28])=[CH:25][CH:26]=3)[NH:21][CH:20]=2)[CH:9]2C(=O)O[C:12](C)([CH3:16])[O:11][C:10]2=[O:18])=[CH:4][CH:3]=1>N1C=CC=CC=1.C(O)C.[Cu]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:19]2[C:27]3[C:22](=[C:23]([CH2:29][S:30][CH3:31])[C:24]([F:28])=[CH:25][CH:26]=3)[NH:21][CH:20]=2)[CH2:9][C:10]([O:11][CH2:12][CH3:16])=[O:18])=[CH:6][CH:7]=1

Participants

5

Reactant 1

HCID 583925085-[(4-Chlorophenyl){6-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}methyl]-2,2-dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 58392255Ethyl 3-(4-chlorophenyl)-3-{6-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}propanoate

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 702EthanolSolventHCID 1049PyridineSolvent

Procedure

23 mg (0.36 mmol) of copper powder were added to 3.31 g (7.16 mmol) of the compound from Example 21A in 13 ml of pyridine and 3 ml of ethanol. The reaction mixture was heated under reflux for 4 h and then the pyridine was removed in vacuo. The residue was taken up in ethyl acetate, silica gel was added, and the mixture was concentrated. The crude product-silica gel mixture was initially prepurified by flash chromatography (mobile phase: cyclohexane/ethyl acetate 5/1→3/1), and the product was again purified by preparative HPLC (acetonitrile/water gradient). 2.38 g (82% of theory) of the title compound were obtained.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 4 h
  3. customthe pyridine was removed in vacuo
  4. additionsilica gel was added
  5. concentrationthe mixture was concentrated
  6. customthe product was again purified by preparative HPLC (acetonitrile/water gradient)

Sources & evidence

ORD record
ord-e49cc1a6ac694d38a8d5dbc85e75cd6c
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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