Toluene → 3-Bromo-7-fluoroquinoline

HRID 2281132Notes

Reaction equation

HRID 2281132 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[CH:18]([Br:21])(Br)Br.[OH-].[Na+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O>[Br:21][C:18]1[CH:7]=[N:8][C:9]2[C:5]([CH:6]=1)=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=2

Participants

7

Reactant 4

HCID 1140TolueneHCID 5558BromoformHCID 14798Sodium HydroxideHCID 3512786-Fluoroindole

Product 1

HCID 712393083-Bromo-7-fluoroquinolineYield 20.6%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

6-Fluoroindole (500 mg, 3.70 mmol) was combined with benzyltriethylammonium chloride (44.4 mg, 0.185 mmol) and toluene (0.32 mL) was added. Bromoform (0.342 mL, 3.70 mmol) was added and the temperature was brought to 40° C. A solution of NaOH (1.110 g, 7.50 mmol) in water (2.22 mL) was then added over 15 minutes. This caused a very dark color to form. The reaction was stirred as a biphasic mixture at 40° C. for 16 h before cooling and partitioning between ethyl acetate and water. The separated aqueous layer was extracted with ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave 3-bromo-7-fluoro-quinoline (171.9 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.93 (d, J=2.1 Hz, 1 H) 8.33 (d, J=2.0 Hz, 1 H) 7.68-7.82 (m, 2 H) 7.39 (td, J=8.6, 2.5 Hz, 1 H); MS (M+1): 226.0.

Workup

  1. additionwas added
  2. customwas brought to 40° C
  3. customto form
  4. temperaturebefore cooling
  5. custompartitioning between ethyl acetate and water
  6. extractionThe separated aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organics dried over MgSO4
  8. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-743369c0338f4600ad24a63793acca6a
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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