Toluene → ethyl 8-carbamoyl-6-(3-methoxyphenyl)-9H-carbazole-2-carboxylate

HRID 2410671Notes

Reaction equation

HRID 2410671 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([C:15](=[O:17])[NH2:16])[CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:7]=[CH:6][C:5]2=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:36][O:37][C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][CH:43]=1>CO.O.C(OCC)(=O)C.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>[C:15]([C:13]1[CH:14]=[C:2]([C:42]2[CH:41]=[CH:40][CH:39]=[C:38]([O:37][CH3:36])[CH:43]=2)[CH:3]=[C:4]2[C:12]=1[NH:11][C:10]1[CH:9]=[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:7]=[CH:6][C:5]2=1)(=[O:17])[NH2:16]

Participants

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 66604694ethyl 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylate

Product 1

HCID 66605544ethyl 8-carbamoyl-6-(3-methoxyphenyl)-9H-carbazole-2-carboxylateYield 49.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of ethyl 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylate (3.5 g, 6.85 mmol, Example 58C), tetrakis(triphenylphosphine)palladium (0)(0.317 g, 0.274 mmol), toluene (30 mL), and 2 M aqueous sodium carbonate (6.85 mL, 13.70 mmol) under nitrogen were added a solution of 3-methoxyphenylboronic acid (1.457 g, 9.59 mmol) in MeOH (4 mL). The resulting reaction mixture was heated at reflux for 5 h. After cooling to room temperature, it was diluted with a mixture of water (250 mL) and ethyl acetate (250 mL) and the two phases were separated. The aqueous phase was extracted with ethyl acetate (2×200 mL), and the combined organic phases were washed with water (2×200 mL), 5% aqueous NH4OH solution (120 mL), and brine (100 mL). The organic phase was dried over Na2SO4 and the solvent removed. The crude material was suspended in a mixture of DCM and ethyl acetate. The solid was collected by filtration, washed with DCM, and air dried to afford 1.31 g product 82A. The filtrate was mixtured with silica gel and the solvent removed. This was loaded onto a silica gel column and eluted with hexane containing 10 to 50% ethyl acetate to afford additional 1.01 g of product for a total of 2.32 g of crude. MS (ESI) m/z 389.2 (M+H). 1H NMR (DMSO-d6) δ ppm 11.73 (1H, s), 8.78 (1H, s), 8.30-8.51 (4H, m), 7.83 (1H, d, J=8.24 Hz), 7.55-7.67 (1H, m), 7.37-7.54 (3H, m), 6.96 (1H, d, J=8.24 Hz), 4.38 (2H, q, J=6.92 Hz), 3.90 (3H, s), 1.39 (3H, t, J=7.02 Hz).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux for 5 h
  4. customthe two phases were separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×200 mL)
  6. washthe combined organic phases were washed with water (2×200 mL), 5% aqueous NH4OH solution (120 mL), and brine (100 mL)
  7. dry with materialThe organic phase was dried over Na2SO4
  8. customthe solvent removed
  9. additionThe crude material was suspended in a mixture of DCM and ethyl acetate
  10. filtrationThe solid was collected by filtration
  11. washwashed with DCM, and air
  12. customdried

Sources & evidence

ORD record
ord-81b281a7e96c45d284c7df4cb63f777a
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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