P-Chloroacetophenone → HCID 58392426, compound

HRID 561440Notes

Reaction equation

HRID 561440 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](O)([CH3:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.CC(C1C=CC(Cl)=CC=1)=O.[Cl-].[In+3].[Cl-].[Cl-].[CH3:31][S:32][CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[C:38]2[C:42]=1[NH:41][CH:40]=[CH:39]2>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:39]2[C:38]3[C:42](=[C:34]([CH2:33][S:32][CH3:31])[CH:35]=[CH:36][CH:37]=3)[NH:41][CH:40]=2)([CH3:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 7467P-ChloroacetophenoneHCID 89439Ethyl 3-(4-chlorophenyl)-3-hydroxybutanoateHCID 159675indium(III)chlorideHCID 583921877-[(Methylsulfanyl)methyl]-1H-indole

Product 1

HCID 58392426HCID 58392426, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

3.42 g (14.10 mmol) of ethyl 3-(4-chlorophenyl)-3-hydroxybutanoate (preparation in analogy to the synthesis of Example 88A starting from 4-chloroacetophenone and ethyl acetate) and 3.12 g (14.10 mmol) of indium(III) chloride were added to 2.50 g (14.10 mmol) of the compound from Example 8A in 100 ml of toluene. The reaction mixture was stirred at 80° C. for 5 h. After cooling to RT, the reaction solution was mixed with water and ethyl acetate, and the solid was filtered off. The phases of the filtrate were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. Purification of the crude product by flash chromatography on silica gel (mobile phase: dichloromethane/methanol 95/5) and then by preparative HPLC (mobile phase: acetonitrile/water gradient) resulted in 0.98 g (17% of theory) of the title compound.

Workup

  1. customto the synthesis of Example 88A
  2. temperatureAfter cooling to RT
  3. filtrationthe solid was filtered off
  4. customThe phases of the filtrate were separated
  5. extractionthe aqueous phase was extracted with ethyl acetate
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude product by flash chromatography on silica gel (mobile phase: dichloromethane/methanol 95/5)

Sources & evidence

ORD record
ord-569ec1b127a54c8e93bf6d49f3f68afb
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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