Hydrochloric Acid → 3,6-Difluorocarbazole

HRID 1776193Notes

Reaction equation

HRID 1776193 reaction equation
CC(C)([O-])C.[Na+].Cl[C:8]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.Cl>C([O-])(=O)C.C([O-])(=O)C.[Pd+2].O1CCOCC1>[F:22][C:20]1[CH:21]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:18]=2[CH:19]=1)=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 23676156Sodium t-butoxideHCID 86702136HCID 86702136, compound

Product 1

HCID 867021373,6-DifluorocarbazoleYield 36.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A reaction tube was charged with sodium tert-butoxide (7.218 g, 75.1 mmol), 2-chloro-4-fluoro-N-(4-fluorophenyl)aniline (3.600 g, 15.0 mmol), tri-tert-butylphosphonium tetrafluoroborate (0.305 g, 1.1 mmol), palladium diacetate (0.169 g, 0.8 mmol), and anhydrous 1,4-dioxane (80 mL). The tube was sealed under nitrogen and heated in an oil bath at 110° C. for 20 hrs. After cooling to room temperature, the mixture was treated with 2M aqueous hydrochloric acid (90 mL) and extracted with methylene chloride (3×50 mL). The combined organic layers were washed with saturated aqueous sodium chloride, dried (anhydrous sodium sulfate), and concentrated in vacuo. The residue was purified by silica gel chromatography (20-50% methylene chloride/hexanes). The solids were rinsed with hexanes and dried to afford pure compound as a white powder (1.1 g, 36%). 1H NMR (300 MHz, CDCl3) δ 7.99 (br s, 1H), 7.67 (dd, 2H, J=8.7, 2.4 Hz), 7.36 (dd, 2H, J=8.7, 4.2 Hz), 7.19 (td, 2H, J=9.0, 2.4 Hz).

Workup

  1. customThe tube was sealed under nitrogen
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with methylene chloride (3×50 mL)
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride
  5. dry with materialdried (anhydrous sodium sulfate)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (20-50% methylene chloride/hexanes)
  8. washThe solids were rinsed with hexanes
  9. customdried

Sources & evidence

ORD record
ord-b115da4e4148423ab69237d13429a849
Source dataset
uspto-grants-2016_02
Patent number
US09265772B2

Reaction notes

Loading…