Potassium Carbonate → Methyl 6-bromo-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylate

HRID 338386Notes

Reaction equation

HRID 338386 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1I.CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[C:31]([OH:36])=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:26][CH:25]=2)O1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:24]1[CH:25]=[CH:26][C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[OH:36])=[CH:28][CH:29]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 592678134'-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-2-olHCID 86698727methyl 6-bromo-5-iodo-1H-indole-3-carboxylate

Product 1

HCID 86698726Methyl 6-bromo-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of methyl 6-bromo-5-iodo-1H-indole-3-carboxylate (100 mg, 0.26 mmol) in toluene (1 ml) and ethanol (1 ml) was added 4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-2-ol (70 mg, 0.24 mmol) followed by aqueous potassium carbonate (2M, 1 ml, 2.0 mmol). The solvent was degassed by passing nitrogen through the system for 5 min. Pd(dppf)Cl2 (10 mg, 0.0053 mmol) was added then sealed and reaction heated to 110° C. The reaction was cooled then partitioned between water and ethyl acetate, then washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo to afford the title compound mixed with unidentified byproducts as a dark tan solid (120 mg). TLC (50% EtOAc/Heptane) indicates no separation between product and byproducts. Crude was taken on to the next step without purification.

Workup

  1. customThe solvent was degassed
  2. customfor 5 min
  3. customthen sealed
  4. customreaction
  5. temperatureThe reaction was cooled
  6. customthen partitioned between water and ethyl acetate
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9eb44053fe3240b0ba4864908a5ed2fe
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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