Bromobenzene → 2-Chloro-5-phenylpyridine

HRID 402585Notes

Reaction equation

HRID 402585 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[CH:8]=[CH:9][C:10]([Cl:13])=[N:11][CH:12]=1.Br[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[NH4+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Pd].C1(C)C=CC=CC=1.O1CCCC1>[Cl:13][C:10]1[N:11]=[CH:12][C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:8][CH:9]=1

Participants

9

Reactant 4

HCID 7961BromobenzeneHCID 25517Ammonium ChlorideHCID 27344145-Bromo-2-chloropyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 27628682-Chloro-5-phenylpyridineYield 68.6%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
10 °C

Procedure

In a 300 mL inner volume flask replaced by nitrogen, 30.3 g of tetrahydrofuran solution containing 19.5% by weight of isopropylmagnesium chloride (57.5 mmol as isopropylmagnesium chloride) as a magnesiation reagent was charged, and cooled at 10° C., and then 20 g of tetrahydrofuran solution containing 5-bromo-2-chloropyridine (9.6 g, 50.0 mmol) as a 2,5-dihalogenopyridine derivative (I), was added dropwise in the range of 10 to 20° C. for 1.0 hour. After adding dropwise, the reaction mixture was stirred in the range of 10 to 20° C. for 1.5 hours, and then added dropwise to the solution of tetrahydrofuran (20 g) containing bromobenzene (7.9 g, 50.0 mmol) as a halogenoaryl derivative (II), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.20 g, 0.25 mmol) as a palladium compound in the range of 10 to 20° C. for 2.0 hours. After adding dropwise, the reaction mixture was stirred in the range of 10 to 20° C. for 4.0 hours, and then saturated aqueous solution of ammonium chloride (50 g) was added. Toluene (50 g) was added to the reaction mixture, and after stirring for 1.0 hour, the reaction mixture was left to stand to separate the organic layer. After washing the organic layer with saturated sodium chloride solution (10 g), it was condensed under reduced pressure to obtain crude 6-chloro-3-phenylpyridine (6.5 g, purity: 82%, yield: 60%). The resultant crude 6-chloro-3-phenylpyridine (6.5 g) was purified by silica gel column chromatography (200 g), and 6-chloro-3-phenylpyridine (4.5 g, yield: 42%) as a 6-halogeno-3-arylpyridine derivative (III) was obtained.

Workup

  1. additionwas charged
  2. additionwas added dropwise in the range of 10 to 20° C. for 1.0 hour
  3. additionAfter adding dropwise
  4. additionAfter adding dropwise
  5. stirringthe reaction mixture was stirred in the range of 10 to 20° C. for 4.0 hours
  6. stirringafter stirring for 1.0 hour
  7. waitthe reaction mixture was left
  8. customto separate the organic layer
  9. washAfter washing the organic layer with saturated sodium chloride solution (10 g), it
  10. customcondensed under reduced pressure

Sources & evidence

ORD record
ord-ba9a4bf62124475c9b6a979c49db894c
Source dataset
uspto-grants-2014_06
Patent number
US08742127B2

Reaction notes

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