1-Bromo-4-fluorobenzene → HCID 67005978, compound

HRID 563389Notes

Reaction equation

HRID 563389 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11]([CH3:16])([CH3:15])[C:12]([OH:14])=[O:13])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.Br[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].N[C@@H]1CCCC[C@H]1N>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cu]I.O1CCOCC1>[F:30][C:27]1[CH:28]=[CH:29][C:24]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([CH:10]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:11]([CH3:16])([CH3:15])[C:12]([OH:14])=[O:13])=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 59252803HCID 59252803, compound

Product 1

HCID 67005978HCID 67005978, compoundYield 56.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3-(1H-indol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid (Example 101(d), 31 mg, 0.11 mmol), 1-bromo-4-fluorobenzene (0.014 mL, 0.13 mmol), copper(I) iodide (4 mg, 0.02 mmol), potassium carbonate (50 mg, 0.36 mmol), trans-1,2-diaminocyclohexane (0.01 mL, 0.08 mmol), tetrabutylammonium iodide (18 mg, 0.05 mmol), and dioxane (0.6 mL) was stirred at 110° C. for 24 h. Concentration and purification using reverse phase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA) gave 3-(1-(4-fluorophenyl)-1H-indol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid (24 mg, 0.062 mmol, 56% yield) as a liquid.

Workup

  1. concentrationConcentration and purification
  2. customphase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)

Sources & evidence

ORD record
ord-46a5de7d5383431c914e4de93fe28ccc
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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