Iodine → 6-Bromo-2-chloro-3-iodoquinoline

HRID 1028932Notes

Reaction equation

HRID 1028932 reaction equation
[Li]CCCC.[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([Cl:17])[CH:11]=[CH:10]2.[I:18]I.C1COCC1.O>C1COCC1.CCCCCC.C(OCC)C.O>[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([Cl:17])[C:11]([I:18])=[CH:10]2

Participants

9

Reactant 4

HCID 807IodineHCID 128940866-Bromo-2-chloroquinolineHCID 21881883Oxolane--water (1/1)HCID 178418339Butyllithium

Product 1

HCID 866768376-Bromo-2-chloro-3-iodoquinoline

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of THF (50 mL) and DIPA (1.8 mL, 12.37 mmol) at −70° C. was added n-BuLi (7.7 mL, 12.4 mmol). The mixture was allowed to stir at 0° C. for 1 h. Slow addition of 6-bromo-2-chloroquinoline (3.0 g, 12.4 mmol) in THF (50 mL) was achieved at −75° C. and the mixture was stirred at this temperature for 2 h. Iodine (3.1 g, 12.4 mmol) in 10 ml of THF was then slowly added and the reaction mixture was allowed to stir at −75° C. for 2 h before hydrolysis by THF/water (20% v/v). Water and diethyl ether were added at −10° C. and the reaction mixture was extracted with ether. The organic layer was washed with sodium thiosulfate and water, dried over MgSO4 and concentrated in vacuo to give a yellow solid which was slurried with hexane and filtered to give 6-bromo-2-chloro-3-iodoquinoline as a tan solid.

Workup

  1. customwas achieved at −75° C.
  2. stirringthe mixture was stirred at this temperature for 2 h
  3. extractionthe reaction mixture was extracted with ether
  4. washThe organic layer was washed with sodium thiosulfate and water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto give a yellow solid which
  8. filtrationfiltered

Sources & evidence

ORD record
ord-70467365e91d4518bf222a527cb517e8
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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