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

HRID 561398Notes

Reaction equation

HRID 561398 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])[CH:24]=[C:25]([F:28])[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])=[C:4]([F:32])[CH:3]=1>N1C=CC=CC=1.C(O)C.[Cu]>[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])[CH:24]=[C:25]([F:28])[CH:26]=3)[NH:21][CH:20]=2)[CH2:9][C:10]([O:11][CH2:12][CH3:16])=[O:18])=[C:4]([F:32])[CH:3]=1

Participants

5

Reactant 1

HCID 583922635-[(4-Chloro-2-fluorophenyl){5-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}methyl]-2,2-dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 58392489Ethyl 3-(4-chloro-2-fluorophenyl)-3-{5-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}propanoate

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 702EthanolSolventHCID 1049PyridineSolvent

Procedure

1.9 mg (0.03 mmol) of copper powder were added to 2.20 g of the compound from Example 16A with a purity of 71% (3.26 mmol) in 25 ml of pyridine and 6.7 ml of ethanol. The reaction mixture was heated under reflux for 1 h. It was concentrated, and the residue was purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient) to result in 1.22 g (88% of theory) of the target compound.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 1 h
  3. concentrationIt was concentrated
  4. customthe residue was purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient)
  5. customto result in 1.22 g (88% of theory) of the target compound

Sources & evidence

ORD record
ord-0cb3537c11da4e598f59054824c5dfe4
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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