Potassium Phosphate, Tribasic → 6-(4-Hydroxy-2-methyl-phenyl)-1,2-dimethyl-1H-indole-3-carboxylic acid methyl ester

HRID 2261844Notes

Reaction equation

HRID 2261844 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10](Cl)=[CH:11][CH:12]=2)[N:7]([CH3:15])[C:6]=1[CH3:16])=[O:4].[CH3:17][C:18]1[CH:19]=[C:20]([OH:33])[CH:21]=[CH:22][C:23]=1B1OC(C)(C)C(C)(C)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:23]3[CH:22]=[CH:21][C:20]([OH:33])=[CH:19][C:18]=3[CH3:17])=[CH:11][CH:12]=2)[N:7]([CH3:15])[C:6]=1[CH3:16])=[O:4]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 574432723-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 574433576-Chloro-1,2-dimethyl-1H-indole-3-carboxylic acid methyl ester

Product 1

HCID 672727366-(4-Hydroxy-2-methyl-phenyl)-1,2-dimethyl-1H-indole-3-carboxylic acid methyl esterYield 88%

Reagents, catalysts & solvents 3

HCID 75806TricyclohexylphosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A flask containing a mixture of 6-chloro-1,2-dimethyl-1H-indole-3-carboxylic acid methyl ester (1.60 g, 6.73 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (3.15 g, 13.5 mmol), aqueous tribasic potassium phosphate (1.27 M, 9.0 mL, 11 mmol), tricyclohexylphosphine (53 mg, 0.19 mmol) and tris(dibenzylideneacetone)dipalladium (0) (73 mg, 0.080 mmol) and dioxane (22 mL) is evacuated and filled with nitrogen several times. The reaction mixture is heated to 100° C. for 18 h. The mixture is allowed to cool and is filtered thru celite, washing with ethyl acetate. The filtrate is concentrated and partitioned with 1 N HCl and ethyl acetate. The ethyl acetate layer is washed with brine, dried over MgSO4 and concentrated. The residue is triturated in THF-heptane to provide 1.83 g (88%) of the title compound as a white solid. MS m/e 310.0 (M+1).

Workup

  1. additionA flask containing
  2. customis evacuated
  3. additionfilled with nitrogen several times
  4. temperatureto cool
  5. filtrationis filtered thru celite
  6. washwashing with ethyl acetate
  7. concentrationThe filtrate is concentrated
  8. custompartitioned with 1 N HCl and ethyl acetate
  9. washThe ethyl acetate layer is washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customThe residue is triturated in THF-heptane

Sources & evidence

ORD record
ord-695807662821476798a683c6d3281e55
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

Loading…