Toluene → 3-Bromo-7-fluoroquinoline

HRID 1424261Notes

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

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, 1H) 8.33 (d, J=2.0 Hz, 1H) 7.68-7.82 (m, 2H) 7.39 (td, J=8.6, 2.5 Hz, 1H); MS (M+1): 226.0.

Workup

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

Sources & evidence

ORD record: ord-2721e39ec42643f784fd6fea243328f5
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927577B2

Reaction notes

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