Sodium Carbonate → 6-Chloro-5-(4-methoxyphenyl)-1H-indole

HRID 1054841Notes

Reaction equation

HRID 1054841 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[Na+].[Na+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.[NH4+].[Cl-]>CCO.C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([CH:5]=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:23]1[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 201262(4-Methoxyphenyl)boronic acidHCID 144196195-Bromo-6-chloro-1H-indole

Product 1

HCID 866986576-Chloro-5-(4-methoxyphenyl)-1H-indoleYield 39.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-bromo-6-chloro-1H-indole (3.20 g, 13.9 mmol), sodium carbonate (3.68 g, 34.7 mmol), and 4-methoxyphenylboronic acid (2.41 g, 15.9 mmol) in EtOH (18 mL), toluene (18 mL) and water (18 mL) was degassed with N2 for 15 minutes, treated with tetrakis(triphenylphosphine)palladium(0) (1.20 g, 0.99 mmol) and heated to 90° C. for 23 hours. The cooled reaction mixture was poured into half-saturated NH4Cl solution (200 mL) and extracted with dichloromethane (3×120 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The resulting dark solid was purified by flash chromatography (5-20% EtOAc/heptane) to give the title compound (1.40 g, 39%) as a white solid. MS (ES+) 258.5 (M+H)+. 1H NMR (500 MHz, CDCl3) δ 8.16 (br. s., 1 H), 7.56 (s, 1 H), 7.42 (d, J=8.1 Hz, 2 H), 7.24 (s, 1 H), 6.98 (d, J=8.1 Hz, 2 H), 6.55 (br. s., 1 H), 3.88 (s, 3 H).

Workup

  1. customwas degassed with N2 for 15 minutes
  2. customThe cooled reaction mixture
  3. extractionextracted with dichloromethane (3×120 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting dark solid was purified by flash chromatography (5-20% EtOAc/heptane)

Sources & evidence

ORD record
ord-257bba41205045a39d04387a345818cb
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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