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

HRID 338497Notes

Reaction equation

HRID 338497 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., 1H), 7.56 (s, 1H), 7.42 (d, J=8.1 Hz, 2H), 7.24 (s, 1H), 6.98 (d, J=8.1 Hz, 2H), 6.55 (br. s., 1H), 3.88 (s, 3H).

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-e467d2c0950a404ab4c41d395f033230
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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