Indole → Indoline

HRID 1099380Notes

Reaction equation

HRID 1099380 reaction equation
FC(F)(F)C(O)=O.C([SiH](CC)CC)C.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16]1.CC(=O)OCC>ClCCl>[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 798IndoleHCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 12052Triethylsilane

Product 1

HCID 10328IndolineYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A round bottom flask containing trifluoroacetic acid (60 mL) was cooled to 0 C under nitrogen and triethylsilane (1.16 g, 1.6 mL, 9.96 mmol) was added followed by the dropwise addition of indole 1 (1.17 g, 3.32 mmol; prepared using a modification of the procedure reported by Macor, et al. J. Med. Chem. 1992, 35, 4503-4505) in 9 mL dry dichloromethane, added over 1 hour. Following complete addition, the solution was stirred for 10 min. Thin layer chromatography (2/1 Hex/EA) indicated no remaining 1. The solvent was removed in vacuo and the residue was dissolved in EtOAc. The organic layer was washed with saturated NaHCO3 (2×), and brine. The EtOAc layer was dried over Na2SO4, filtered, and concentrated. Purification by column chromatography on silica gel (2/1 hexane/ethyl acetate) afforded 2 as a yellow oil (0.79 g, 67%). 1H NMR (CDCl3, 300 MHz) δ7.34-7.31 (m, 5H) 6.99-6.85 (m, 1H)/6.34-6.27 (m, 2H), 5.12 (s, 2H), 4.13-3.71 (m, 2H), 3.58-3.16 (m, 5H), 2.05-1.87 (m, 4H), 1.73-1.57 (m, 2H) ppm.

Workup

  1. temperaturewas cooled to 0 C under nitrogen
  2. customprepared
  3. additionaddition
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in EtOAc
  6. washThe organic layer was washed with saturated NaHCO3 (2×), and brine
  7. dry with materialThe EtOAc layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by column chromatography on silica gel (2/1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c39e6becb0284eb2a72f71ab2d48ff61
Source dataset
uspto-grants-2012_03
Patent number
US08143426B2

Reaction notes

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