Bromoform → 3-Bromo-6-fluoroquinoline

HRID 2281137Notes

Reaction equation

HRID 2281137 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[OH-].[Na+].[CH:13]([Br:16])(Br)Br>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C1(C)C=CC=CC=1.O>[Br:16][C:13]1[CH:6]=[N:7][C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2

Participants

7

Reactant 3

HCID 5558BromoformHCID 14798Sodium HydroxideHCID 678615-Fluoroindole

Product 1

HCID 181862043-Bromo-6-fluoroquinolineYield 15%

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 5-Fluoroindole (2.00 g, 14.8 mmol) and benzyltriethylammonium chloride (168.5 mg, 0.740 mmol) in toluene (3.00 mL) and bromoform (3.00 mL) at 40° C. was added a solution of sodium hydroxide (4.44 g, 111 mmol) in water (12.0 mL) in a dropwise manner. The reaction then stirred at 40° C. for 48 h. After cooling, the solvent was evaporated and the residue was diluted with methyl tert-butyl ether (100 mL) and water (100 mL). The aqueous layer was extracted with methyl tert-butyl ether. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give 2.00 g of crude material. Purification by silica gel flash chromatography (0-2% ethyl acetate in petroleum ether) provided 3-bromo-6-fluoroquinoline (503 mg, 15% yield) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.87 (d, J=2.0 Hz, 1H), 8.27 (d, J=2.0 Hz, 1H), 8.08 (dd, J=9.2, 5.6 Hz, 1H), 7.52-7.41 (m, 1H), 7.35 (dd, J=8.8, 2.8 Hz, 1H). (M+1): 225.6.

Workup

  1. customThe reaction
  2. temperatureAfter cooling
  3. customthe solvent was evaporated
  4. additionthe residue was diluted with methyl tert-butyl ether (100 mL) and water (100 mL)
  5. extractionThe aqueous layer was extracted with methyl tert-butyl ether
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give 2.00 g of crude material
  9. customPurification by silica gel flash chromatography (0-2% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-d3320601d06b409fa4474cf05d0e72af
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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