Carbazole → 9-(oxiran-2-ylmethyl)-9H-carbazole

HRID 1776165Notes

Reaction equation

HRID 1776165 reaction equation
[OH-].[K+].[CH:3]1[C:15]2[NH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH2:16]([CH:18]1[O:20][CH2:19]1)Br>CN(C)C=O>[O:20]1[CH2:19][CH:18]1[CH2:16][N:14]1[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:7]2[C:15]1=[CH:3][CH:4]=[CH:5][CH:6]=2

Participants

5

Reactant 3

HCID 6854CarbazoleHCID 14797Potassium HydroxideHCID 18430Epibromohydrin

Product 1

HCID 27755079-(oxiran-2-ylmethyl)-9H-carbazoleYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Powdered potassium hydroxide (3.36 g, 60 mmol) was added to a solution of carbazole (8.36 g, 50 mmol) in anhydrous N,N-dimethylformamide (50 mL) and stirred at ambient temperature for 1 hour. The reaction mixture was cooled in an ice bath and epibromohydrin (10.3 mL, 125 mmol) was added. The ice bath was removed and the reaction was stirred at room temperature for 20 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was washed successively with water and saturated aqueous sodium chloride solutions, dried (anhydrous sodium sulfate), filtered, and concentrated. The crude material was triturated with hexanes, and recrystallized from ethyl acetate/hexanes to yield the desired product as white needles (6.41 g, 58% yield). A second crop of crystals was crystallized from the mother liquor to give additional product (1.2 g, 11%). 1H NMR (CDCl3, 300 MHz) δ 8.11-8.08 (m, 2H), 7.46-7.44 (m, 4H), 7.28-7.25 (m, 2H), 4.68-4.62 (dd, 1H, J=3.1, 15.8 Hz) 4.45-4.38 (dd, 1H, J=4.8, 15.9 Hz), 3.37 (m, 1H), 2.84-2.81 (dd, 1H, J=4.2, 4.3 Hz), 2.60-2.57 (dd, 1H, J=2.5, 5.0 Hz). HPLC analysis: (C18, 5-95% acetonitrile in H2O+0.1% trifluoroacetic acid over 20 min: detention time, % area at 254 nm): 7.83 min, 98.7%.

Workup

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. customThe ice bath was removed
  3. stirringthe reaction was stirred at room temperature for 20 hours
  4. customThe mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed successively with water and saturated aqueous sodium chloride solutions
  6. dry with materialdried (anhydrous sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was triturated with hexanes
  10. customrecrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4b1e3467195e4d4db357cb8f2ac93346
Source dataset
uspto-grants-2016_02
Patent number
US09265772B2

Reaction notes

Loading…