Dimethylformamide → Methyl 4-(4-fluorophenyl)-1-methyl-1H-indole-6-carboxylate

HRID 1047646Notes

Reaction equation

HRID 1047646 reaction equation
Br[C:2]1[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[CH3:15].[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(NC(C)C)(C)C.CN(C)C=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Na+].[Na+].[Na+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.C(OCC)(=O)C.O>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:2]2[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]3[C:3]=2[CH:4]=[CH:5][N:6]3[CH3:15])=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 2856454-Fluorophenylboronic acidHCID 58051755methyl 4-bromo-1-methyl-1H-indole-6-carboxylate

Product 1

HCID 66661499Methyl 4-(4-fluorophenyl)-1-methyl-1H-indole-6-carboxylateYield 85.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of methyl 4-bromo-1-methyl-1H-indole-6-carboxylate (0.45 g, 1.69 mmol), (4-fluorophenyl)-boronic acid (0.36 g, 2.53 mmol), 3,3′,3″-phosphinidynetris (benzensulfonic acid) trisodium salt (81.0 mg, 0.13 mmol), palladium(II) acetate (9.5 mg, 0.04 mmol) and diisopropylamine (0.60 mL, 4.22 mmol) were added N,N-dimethylformamide (6.3 mL) and water (2.1 mL). The mixture was heated to 80° C. for 1 h. The mixture was cooled to ambient temperature and ethyl acetate was added. The organic layer was washed with water (3×10 mL), saturated aqueous sodium chloride (1×10 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate) gave the title compound (0.41 g): LC-MS [M+1]=284.1.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. washThe organic layer was washed with water (3×10 mL), saturated aqueous sodium chloride (1×10 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-61aec917a638428c9699c41224bb7a22
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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