Potassium Phosphate, Tribasic → Methyl 1-(3,4-difluorophenyl)-indole-5-carboxylate

HRID 409922Notes

Reaction equation

HRID 409922 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.I[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([F:22])[CH:16]=1.CN[C@@H]1CCCC[C@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(Cl)Cl.[Cu]I>[F:21][C:18]1[CH:19]=[C:20]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[CH:15]=[CH:16][C:17]=1[F:22]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27244441,2-Difluoro-4-iodobenzeneHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 2737635methyl 1H-indole-5-carboxylate

Product 1

HCID 59626069Methyl 1-(3,4-difluorophenyl)-indole-5-carboxylateYield 91.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of methyl indole-5-carboxylate 24a (2 g, 11.4 mmol), 1-iodo-3,4-difluoro-benzene 24b (1.5 mL, 12.5 mmol), CuI (0.22 g, 1.14 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (0.54 mL, 3.43 mmol), and K3PO4 (6.06 g, 28.5 mmol) in toluene (12 mL) was heated at 110° C. for 7 hours. The reaction mixture was diluted with CH2Cl2 and filtered. The solution was concentrated and the residue was purified by flash column chromatography (silica gel, 20% EtOAc/heptane) to give 24c (3.0 g).

Workup

  1. filtrationfiltered
  2. concentrationThe solution was concentrated
  3. customthe residue was purified by flash column chromatography (silica gel, 20% EtOAc/heptane)

Sources & evidence

ORD record
ord-73230c54416347769bdb61091e53589d
Source dataset
uspto-grants-2014_06
Patent number
US08759533B2

Reaction notes

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