Trifluoroacetic acid → 1H-Indole, 5-fluoro-3-(4-pyridinylmethyl)-

HRID 1166185Notes

Reaction equation

HRID 1166185 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]([C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)O.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 11322446(5-fluoro-1H-indol-3-yl)-pyridin-4-yl-methanol

Product 1

HCID 118169851H-Indole, 5-fluoro-3-(4-pyridinylmethyl)-

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of (5-fluoro-1H-indol-3-yl)-pyridin-4-yl-methanol (3.36 g, 13.9 mmol) in methylene chloride is treated with triethylsilane (2.48 ml, 15.5 mmol) followed by trifluoroacetic acid (11.9 ml, 155 mmol) at room temperature, stirred overnight and concentrated in vacuo. The resultant residue is treated with saturated Na2CO3 to pH>9 and extracted with methylene chloride. The combined extracts are washed sequentially with water and brine, dried over Na2SO4 and concentrated in vacuo. This residue is purified by flash chromatography (silica gel, CH2Cl2/MeOH: 95/5) to give the title product as a white solid, 2.5 g (80%) mp 141-142° C. (lit. mp 149° C., Malleron et al, J. Med. Chem. 1993, 36, 1194).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe resultant residue is treated with saturated Na2CO3 to pH>9
  3. extractionextracted with methylene chloride
  4. washThe combined extracts are washed sequentially with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThis residue is purified by flash chromatography (silica gel, CH2Cl2/MeOH: 95/5)

Sources & evidence

ORD record
ord-264690e4c5fa4d2f81f2af34135280c3
Source dataset
uspto-grants-2003_09
Patent number
US06613781B2

Reaction notes

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