Calcium Carbonate → 6-Chloro-2-(4-fluorophenyl)-1H-indole

HRID 1016645Notes

Reaction equation

HRID 1016645 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH:8]=1)[NH2:7].[C:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)#[CH:11].C(=O)([O-])[O-].[Ca+2]>C(NCC)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.[Cu]I>[Cl:1][C:2]1[CH:8]=[C:6]2[C:5]([CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[NH:7]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10112Calcium CarbonateHCID 5226271-Ethynyl-4-fluorobenzeneHCID 6396975-Chloro-2-iodoaniline

Product 1

HCID 184070336-Chloro-2-(4-fluorophenyl)-1H-indoleYield 85%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418397HCID 178418397, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

A mixture of 5-chloro-2-iodoaniline (33.0 g, 0.13 mol) and 1-ethynyl-4-fluorobenzene (26.4 g, 0.22 mol) in diethylamine (400 mL) was degassed with bubbling nitrogen for 20 min., then tetrakis(triphenylphosphine)palladium(0) (2.0 g, 1.7 mmol) and copper (I) iodide (170 mg, 0.9 mmol) were added and the mixture was stirred at room temperature for 12 h. The solvent was evaporated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with water (2×), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in dimethylformamide (250 mL), calcium carbonate (13 g, 0.13 mol) and copper (I) iodide (12.4 g, 0.07 mol) were added and the mixture was stirred at 120° C. for 22 h. The mixture was cooled, filtered and the solvent was evaporated under reduced pressure. Water was added and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with water (2×) and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with ether/hexane and the solid was collected and dried in vacuo to give the title compound (25.4 g, 85%). 1H NMR (360 MHz, CDCl3) δ 7.59 (2H, m), 7.49 (1H, d, J 8.5 Hz), 7.44 (1H, s), 7.24-6.99 (3H, m), and 6.69 (1H, d, J 1.8 Hz).

Workup

  1. customwas degassed with bubbling nitrogen for 20 min.
  2. customThe solvent was evaporated under reduced pressure, water
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe combined organic fractions were washed with water (2×)
  6. dry with materialdried (MgSO4)
  7. customthe solvent was evaporated under reduced pressure
  8. dissolutionThe residue was dissolved in dimethylformamide (250 mL)
  9. stirringthe mixture was stirred at 120° C. for 22 h
  10. temperatureThe mixture was cooled
  11. filtrationfiltered
  12. customthe solvent was evaporated under reduced pressure
  13. additionWater was added
  14. extractionthe mixture was extracted with ethyl acetate
  15. washThe combined organic fractions were washed with water (2×) and brine
  16. dry with materialdried (MgSO4)
  17. customthe solvent was evaporated under reduced pressure
  18. customThe residue was triturated with ether/hexane
  19. customthe solid was collected
  20. customdried in vacuo

Sources & evidence

ORD record
ord-4efa7ef293a542eca902132c550cedb2
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

Loading…