Ethyl Acetoacetate → ethyl 4-(1-ethoxy-1,3-dioxobutan-2-yl)-7-o-tolyl-1H-indole-2-carboxylate

HRID 2199740Notes

Reaction equation

HRID 2199740 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])=[C:7]2[C:3]=1[CH:4]=[C:5]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[NH:6]2.[O:23]=[C:24]([CH3:31])[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:29]([O:28][C:26](=[O:27])[CH:25]([C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])=[C:7]2[C:3]=1[CH:4]=[C:5]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[NH:6]2)[C:24](=[O:23])[CH3:31])[CH3:30]

Participants

7

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 62657Potassium Phosphate, TribasicHCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 68936971ethyl 4-chloro-7-o-tolyl-1H-indole-2-carboxylate

Product 1

HCID 68940072ethyl 4-(1-ethoxy-1,3-dioxobutan-2-yl)-7-o-tolyl-1H-indole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
93 °C

Procedure

A mixture of ethyl 4-chloro-7-o-tolyl-1H-indole-2-carboxylate (EXAMPLE 166C) (0.93 g), ethyl 3-oxobutanoate (0.849 g), di-tert-butyl(2′-methylbiphenyl-2-yl)phosphine (0.093 mg), K3PO4 (3.46 g), and palladium(II) acetate (0.033 g) in toluene (8 mL) was degassed via vacuum/nitrogen cycle three times. The reaction mixture was heated at 93° C. for 14 hours. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with additional ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified with flash chromatography on silica gel (ethyl acetate in hexanes) to give the title compound.

Workup

  1. customwas degassed via vacuum/nitrogen cycle three times
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with additional ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified with flash chromatography on silica gel (ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a34fa489b17d4b3bb98e453bcb57452c
Source dataset
uspto-grants-2016_06
Patent number
US09359296B2

Reaction notes

Loading…