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

HRID 397615Notes

Reaction equation

HRID 397615 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 acid2×HCID 12052TriethylsilaneHCID 11322446(5-fluoro-1H-indol-3-yl)-pyridin-4-yl-methanol

Product 1

HCID 118169851H-Indole, 5-fluoro-3-(4-pyridinylmethyl)-Yield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of (5-fluoro-1H-indol-3-yl)-pyridin-4-yl-methanol (0.799 g, 3.3 mmol) in methylene chloride (13 mL) was added triethylsilane (0.60 mL, 3.7 mmol) followed by trifluoroacetic acid (2.85 mL, 37 mmol) at room temperature. After addition of trifluoroacetic acid, a clear black solution was obtained. The reaction mixture was stirred overnight and the solvent and excess trifluoroacetic acid was removed on a rotary evaporator. To the residue was added saturated Na2CO3 to adjust the pH>9. The aqueous layer was extracted with methylene chloride and the combined organic extracts was washed with water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography (methylene chloride to methylene chloride/ethyl acetate to ethyl acetate, 100% to 50% to 100%) to give 0.56 g (75%) of a solid: mp 141-142° C. [(mp 149° C.; previously reported in J. Med. Chem. 36, 1194 (1993)].

Workup

  1. customa clear black solution was obtained
  2. customthe solvent and excess trifluoroacetic acid was removed on a rotary evaporator
  3. additionTo the residue was added saturated Na2CO3
  4. extractionThe aqueous layer was extracted with methylene chloride
  5. washthe combined organic extracts was washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel column chromatography (methylene chloride to methylene chloride/ethyl acetate to ethyl acetate, 100% to 50% to 100%)

Sources & evidence

ORD record
ord-00d502228e134326b8915fcf963c34f3
Source dataset
uspto-grants-2003_08
Patent number
US06610712B2

Reaction notes

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