2-Bromopyridine → HCID 86641648, compound

HRID 220446Notes

Reaction equation

HRID 220446 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([N-]C(C)C)(C)C.[Li+].[F:16][C:17]1[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=1>O1CCCC1.C(=O)(O)[O-].[Na+].[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[C:7]([C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 79732-BromopyridineHCID 96054-FluoroiodobenzeneHCID 2724682Lithium diisopropylamide

Product 1

HCID 86641648HCID 86641648, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve 2-bromopyridine (5 mL, 51.3 mmol) in tetrahydrofuran (125 mL). Cool to −78° C. and add lithium diisopropylamide (28.2 mL, 56.4 mmol, 2 M solution in heptane/tetrahydrofuran/ethylbenzene). Stir for 45 min. at −78° C., add zinc chloride (102.5 mL, 51.3 mmol, 0.5 M solution in tetrahydrofuran) and warm to 25° C. for one hr. Add 1-fluoro-4-iodobenzene (5.91 mL, 51.3 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (2.96 g, 2.56 mmol) and reflux the mixture for 18 hr. Cool the mixture to room temperature, dilute with saturated aqueous sodium bicarbonate and extract 3 times with DCM. Combine the organic extracts, dry (sodium sulfate), filter and purify (silica gel chromatography, eluting with 20:80 ethyl acetate:hexanes) to give 2-bromo-3-(4-fluorophenyl)-pyridine (4.27 g, 33% yield).

Workup

  1. temperaturewarm to 25° C. for one hr
  2. temperatureCool the mixture to room temperature
  3. extractionextract 3 times with DCM
  4. dry with materialdry (sodium sulfate)
  5. filtrationfilter
  6. custompurify
  7. wash(silica gel chromatography, eluting with 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-0b4632084e634999be1a259f02dcdb0e
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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