Carbazole → 4-(2-Carbazol-9-yl-ethyl)benzoic acid methyl ester

HRID 403642Notes

Reaction equation

HRID 403642 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+].[H][H].[CH3:18][O:19][C:20](=[O:30])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28]Br)=[CH:23][CH:22]=1>CN(C=O)C.C(OCC)(=O)C>[CH3:18][O:19][C:20](=[O:30])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][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:23][CH:22]=1

Participants

7

Reactant 4

HCID 6854CarbazoleHCID 24758Sodium hydrideHCID 10586287Methyl 4-(2-bromoethyl)benzoateHCID 178418361HCID 178418361, compound

Product 1

HCID 668730964-(2-Carbazol-9-yl-ethyl)benzoic acid methyl esterYield 43%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Carbazole (0.50 g, 2.99 mmol) and sodium hydride (60 wt. % in mineral oil, 0.14 g, 3.59 mmol) were placed under argon and dissolved in 6 mL of anhydrous DMF at room temperature, giving a dark brown solution. Following the evolution of hydrogen gas, 4-(2-bromo-ethyl)benzoic acid methyl ester (26) (0.73 g, 2.99 mmol) in DMF (2 mL) was added and the reaction was stirred at 70° C. for 2 h. The mixture was taken up in ethyl acetate (30 mL) and water (30 mL), the organic layer was separated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (2×25 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O). The product co-eluted with unreacted carbazole. Cold MeOH (8 mL) was added to the product mixture and the suspension was filtered to remove the solid carbazole. The filtrate was concentrated to give the title compound (291 mg, 43%) as a red solid. 1H NMR (400 MHz, CDCl3): δ 8.11 (m, 2H), 7.92 (d, 2H, J=8.0 Hz), 7.43 (m, 2H), 7.30 (m, 2H), 7.25 (m, 4H), 4.55 (t, 2H, J=7.3 Hz), 3.91 (s, 3H), 3.20 (t, 2H, J=7.4 Hz). 13C NMR (100 MHz, CDCl3): δ 167.0, 144.1, 140.1, 123.0, 128.9, 125.8, 122.9, 120.4, 119.4, 110.6, 108.4, 52.1, 44.4, 35.2. ESI-HRMS (m/z): [M+H]+ calcd. for C22H19NO2, 330.1489. found, 330.1460.

Workup

  1. customgiving a dark brown solution
  2. additionwas added
  3. customwater (30 mL), the organic layer was separated
  4. extractionthe aqueous layer extracted with ethyl acetate (2×10 mL)
  5. washThe combined organic layers were washed with brine (2×25 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O)
  9. additionCold MeOH (8 mL) was added to the product mixture
  10. filtrationthe suspension was filtered
  11. customto remove the solid carbazole
  12. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-4d4acb2a0f7b439cb29a6460bc4df813
Source dataset
uspto-grants-2014_06
Patent number
US08748451B2

Reaction notes

Loading…