Hydrochloric Acid → 5-[1-(4-Fluoro-phenyl)-1H-indol-5-yl]-pent-4-yn-1-ol

HRID 1633634Notes

Reaction equation

HRID 1633634 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13](OS(C(F)(F)F)(=O)=O)=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:4][CH:3]=1.[CH2:25]([OH:30])[CH2:26][CH2:27][C:28]#[CH:29].Cl>N1CCCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu](I)I>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:29]#[C:28][CH2:27][CH2:26][CH2:25][OH:30])=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 793464-Pentyn-1-ol2×HCID 86585583Trifluoro-methanesulfonic acid 1-(4-fluoro-phenyl)-1H-indol-5-yl ester

Product 1

HCID 186795225-[1-(4-Fluoro-phenyl)-1H-indol-5-yl]-pent-4-yn-1-olYield 96.4%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8082PiperidineSolvent

Procedure

To 2.25 g (6.25 mmol) Trifluoro-methanesulfonic acid 1-(4-fluoro-phenyl)-1H-indol-5-yl ester in 12.5 ml piperidine were added 360 mg (0.31 mmol) tetrakis(triphenylphosphine)-palladium followed by 60.0 mg (0.31 mmol) copper iodide. The solution was evaporated and flushed with argon prior to the addition of 450 μl (4.95 mmol) 4-pentynol at 80° C. over a period of 45 min. Further 0.45 ml (4.95 mmol) 4-pentynol were added and the solution was stirred for 2 h. The mixture was added to ice water, acidified with 2M HCl and extracted with ether. The combined organic phases were washed with water and dried over Na2SO4. Purification by column chromatography with CH2Cl2/MeOH 19:1 yielded 1.4 g (76%) 5-[1-(4-Fluoro-phenyl)-1H-indol-5-yl]-pent-4-yn-1-ol as light yellow waxy solid, MS: 293 (M).

Workup

  1. customThe solution was evaporated
  2. customflushed with argon
  3. extractionextracted with ether
  4. washThe combined organic phases were washed with water
  5. dry with materialdried over Na2SO4
  6. customPurification by column chromatography with CH2Cl2/MeOH 19:1

Sources & evidence

ORD record
ord-67979a05947a4dcb877c09d871428e19
Source dataset
uspto-grants-2003_01
Patent number
US06503907B2

Reaction notes

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