1,3-Difluorobenzene → 6-(2,6-Difluorophenyl)-quinoline

HRID 980198Notes

Reaction equation

HRID 980198 reaction equation
C([Li])CCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.Br[C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[CH:18]2>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[CH:18]2

Participants

6

Reactant 3

HCID 97411,3-DifluorobenzeneHCID 792436-BromoquinolineHCID 178418339Butyllithium

Product 1

HCID 137730476-(2,6-Difluorophenyl)-quinolineYield 88%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.55 M solution of n-butyllithium (40 ml) in hexanes was added dropwise to a stirred solution of 1,3-difluorobenzene (5.7 g) in 150 ml of dry tetrahydrofuran at -78° C. After one hour at -78° C. a solution of anhydrous zinc chloride (10.22 g) in 40 ml of tetrahydrofuran was added. After a further 10 minutes at -78° C., 9.36 g (45 mmoles) 6-bromoquinoline was added neat followed by tetrakistriphenylphosphine palladium (2.5 g, 2.16 mmoles). The solution was then allowed to warm slowly to room temperature and heated to 40° C. for 12 hours. The mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The pH was adjusted to 9 and the product was extracted with ethyl acetate, dried over MgSO4 ; filtered and concentrated in vacuo to give a white solid (9.5 g, 88%) of m.p. 112°-113° C.

Workup

  1. temperatureheated to 40° C. for 12 hours
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched with saturated aqueous ammonium chloride
  4. extractionthe product was extracted with ethyl acetate
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4cc3d4060a0844a5ac0ac0aa5ed55d54
Source dataset
uspto-grants-1987_01
Patent number
US04636506

Reaction notes

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