Toluene → 2-cyclopropyl-5-fluoro-1H-indole

HRID 2382130Notes

Reaction equation

HRID 2382130 reaction equation
[CH:1]1([C:4]#[C:5][NH:6][C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[CH2:3]C1.[C:14]1(C)C=CC=CC=1>[Cl-].[Na+].O>[CH:4]1([C:5]2[NH:6][C:7]3[C:8]([CH:14]=2)=[CH:9][C:10]([F:13])=[CH:11][CH:12]=3)[CH2:1][CH2:3]1

Participants

4

Reactant 2

HCID 1140TolueneHCID 685573712-Cyclopropylethynyl-4-fluoro-phenylamine

Product 1

HCID 685530852-cyclopropyl-5-fluoro-1H-indoleYield 78%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2-cyclopropylethynyl-4-fluoro-phenylamine (0.80 g, 4.5 mmol) in PhMe (16 mL) is treated with InBr3 (80 mg, 0.23 mmol) and stirred at 110° C. for 0.5 h. The mixture is then poured over brine (20 mL), and extracted with EtOAc (3×20 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0%-25% EtOAc in heptane to afford 2-cyclopropyl-5-fluoro-1H-indole (610 mg, 78%). MS: 176 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.88 (s, NH, 1H), 7.12 (m, 2H), 6.83 (m, 1H), 6.09 (s, 1H), 1.90 (m, 1H), 0.95 (m, 2H), 0.77 (m, 2H).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organic layer is dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel chromatography
  6. washeluting with 0%-25% EtOAc in heptane

Sources & evidence

ORD record
ord-6dd0d72d2c7b452398a452a9154cfe54
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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