1,3-Difluorobenzene → HCID 10899450, compound

HRID 2291669Notes

Reaction equation

HRID 2291669 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:20]=[CH:19][N:18]=[CH:17][CH:16]=1>O1CCCC1.CCOCC.[Cl-].[Zn+2].[Cl-].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1

Participants

8

Reactant 3

HCID 97411,3-DifluorobenzeneHCID 142684-BromopyridineHCID 178418339Butyllithium

Product 1

HCID 10899450HCID 10899450, compoundYield 73%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-50 °C

Procedure

A 1.6M solution of n-butyl lithium (14 ml) was added dropwise to a stirred solution of 1,3-difluorobenzene (2.17 g) in 34 ml dry tetrahydrofuran at -78° C. After 1 hour at -78° C., the solution was warmed to -50° C. and a solution of anhydrous zinc chloride (3.0 g) in 34 ml tetrahydrofuran was added. After a further 20 minutes at -50° C., a solution of 4-bromopyridine (1.62 g) in 10 ml ether was added, followed by 1.0 g of tetrakis(triphenylphosphine) palladium. The solution was then allowed to warm slowly to room temperature and it was then heated at 40° C. for 12 hours. The mixture was cooled to room temperature and it was first quenched with saturated aqueous ammonium chloride and then extracted with ethyl acetate. The organic extracts were dried and evaporated yielding a yellow crystalline solid. This material was purified by elution on silica gel with ethyl acetate/hexanes to give 1.4 g (73% yield) of the required product as a pale yellow solid of m.p. 113°-114° C. NMR (CDC13, 60 MHz): 8.65 (m, 2H), 6.8-7.6 (m, 5H).

Workup

  1. waitAfter a further 20 minutes at -50° C.
  2. temperatureto warm slowly to room temperature
  3. temperatureit was then heated at 40° C. for 12 hours
  4. temperatureThe mixture was cooled to room temperature
  5. customit was first quenched with saturated aqueous ammonium chloride
  6. extractionextracted with ethyl acetate
  7. customThe organic extracts were dried
  8. customevaporated
  9. customyielding a yellow crystalline solid
  10. customThis material was purified by elution on silica gel with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-3f5ac86970a14dc1b01b2d4ce221c89d
Source dataset
uspto-grants-1989_01
Patent number
US04797490

Reaction notes

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