Calcium Carbonate → HCID 18403250, compound

HRID 1017198

Reaction equation

HRID 1017198 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH:8]=1)[NH2:7].[F:10][C:11]1[CH:12]=[C:13]([C:17]#[CH:18])[CH:14]=[CH:15][CH:16]=1.C(=O)([O-])[O-].[Ca+2]>C(NCC)C.[Cu]I>[F:10][C:11]1[CH:12]=[C:13]([C:17]2[NH:7][C:6]3[C:5]([CH:18]=2)=[CH:4][CH:3]=[C:2]([F:1])[CH:8]=3)[CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 10112Calcium CarbonateHCID 5202181-Ethynyl-3-fluorobenzeneHCID 27745125-Fluoro-2-iodoaniline

Product 1

HCID 18403250HCID 18403250, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8021DiethylamineSolvent

Procedure

5-Fluoro-2-iodoaniline (30 g, 126 mmol) and 3-fluorophenylacetylene (20 g, 166 mmol) were dissolved in diethylamine (500 ml) and the mixture purged with nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added and the mixture stirred at room temperature for 15 h. The solvent was removed in vacuo and the residue partitioned between diethyl ether (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml), saturated sodium chloride (200 ml), dried over MgSO4, filtered through a short plug of Florisil and evaporated in vacuo. The solid was dissolved in anhydrous DMF (500 ml), copper(I) iodide (12 g, 63 mmol) and calcium carbonate (12.6 g, 126 mmol) added and the mixture heated at 120° C. under an atmosphere of nitrogen for 48 h. The mixture was filtered through hyflo and the filtrate evaporated in vacuo. The residue was partitioned between ethyl acetate (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml) and saturated sodium chloride (100 ml), dried over MgSO4 and evaporated in vacuo. The residue was triturated with a mixture of diethyl ether and hexane, the solid filtered and dried in vacuo to afford 25 g (109 mmol; 87%) of 2-(3-fluorophenyl)-6-fluoroindole as a brown solid. δH (360 MHz; CDCl3) 6.78 (1H, d, J 1.8, indole H3), 6.88 (1H, m, aromatic), 6.99 (1H, m, aromatic), 7.05 (1H, dd, J 9.5 and 2.2, aromatic), 7.29 (1H, dd, J 8.6 and 1.0, aromatic), 7.36 (2H, m, aromatics), 7.51 (1H, dd, J 8.6 and 5.3, indole H4), 8.37 (1H, br s, NH).

Workup

  1. customthe mixture purged with nitrogen for 10 min
  2. additionTetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between diethyl ether (500 ml) and water (500 ml)
  5. customthe organic layer was separated
  6. washwashed with water (2×500 ml), saturated sodium chloride (200 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered through a short plug of Florisil
  9. customevaporated in vacuo
  10. dissolutionThe solid was dissolved in anhydrous DMF (500 ml)
  11. temperaturethe mixture heated at 120° C. under an atmosphere of nitrogen for 48 h
  12. filtrationThe mixture was filtered through hyflo
  13. customthe filtrate evaporated in vacuo
  14. customThe residue was partitioned between ethyl acetate (500 ml) and water (500 ml)
  15. customthe organic layer was separated
  16. washwashed with water (2×500 ml) and saturated sodium chloride (100 ml)
  17. dry with materialdried over MgSO4
  18. customevaporated in vacuo
  19. customThe residue was triturated with a mixture of diethyl ether and hexane
  20. filtrationthe solid filtered
  21. customdried in vacuo

Sources & evidence

ORD record
ord-0794dc0fd90848b7b2c16a921b14e360
Source dataset
uspto-grants-2002_11
Patent number
US06479480B1

Linked notes

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