Carbazole → 4-Carbazol-9-ylmethylbenzoic acid methyl ester

HRID 1970815Notes

Reaction equation

HRID 1970815 reaction equation
[CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:16][O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([CH2:25]Br)=[CH:21][CH:20]=1>CN(C=O)C.[I-].[K+]>[CH3:16][O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([CH2:25][N:12]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]3[C:13]2=[CH:1][CH:2]=[CH:3][CH:4]=3)=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 6854CarbazoleHCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoate

Product 1

HCID 668730724-Carbazol-9-ylmethylbenzoic acid methyl esterYield 50.2%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

Carbazole (1.0 g, 6.0 mmol) and sodium hydride (60 wt. % in mineral oil, 0.14 g, 6.0 mmol) were placed under argon and dissolved in 5 mL of DMF. The mixture was stirred at room temperature for 30 min, followed by addition of 4-bromomethylbenzoic acid methyl ester (1.4 g, 6.0 mmol) and 5 mg of potassium iodide. The reaction was heated to 80° C. for 2 h upon which a precipitate formed and the reaction turned from dark brown to dark orange. The reaction was then quenched with water (30 mL) and ethyl acetate (30 mL). The organic layer was isolated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water (2×20 mL), brine (15 mL), dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography (0-80% gradient of ethyl acetate in hexane) afforded the title compound (0.95 g, 50%) as a light yellow solid. 1H NMR (400 MHz, DMSO): δ 8.19 (d, 2H, J=7.7 Hz), 7.51 (d, 2H, J=8.3 Hz), 7.41 (m, 4H), 7.23 (m, 4H), 5.74 (s, 2H), 3.79 (s, 3H). 13C NMR (100 MHz, DMSO): δ 166.4, 143.8, 129.9, 127.3, 126.4, 125.9, 120.8, 119.6, 118.9, 111.4, 109.9, 52.5, 45.8. ESI-HRMS (m/z): [M+H]+ calcd. for C21H17NO2, 316.1323. found, 316.1314.

Workup

  1. temperatureThe reaction was heated to 80° C. for 2 h upon which a precipitate
  2. customformed
  3. customThe reaction was then quenched with water (30 mL) and ethyl acetate (30 mL)
  4. customThe organic layer was isolated
  5. extractionthe aqueous layer extracted with ethyl acetate (2×10 mL)
  6. washThe combined organic layers were washed with water (2×20 mL), brine (15 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (0-80% gradient of ethyl acetate in hexane)

Sources & evidence

ORD record
ord-0d61bfa5157d4df0bd03356d6edcfea8
Source dataset
uspto-grants-2013_04
Patent number
US08431538B2

Reaction notes

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