2-Bromopyridine → 6'-Chloro-[2,3']bipyridinyl

HRID 402586Notes

Reaction equation

HRID 402586 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][N: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].O1CCCC1>[Cl:13][C:10]1[N:11]=[CH:12][C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 79732-BromopyridineHCID 25517Ammonium ChlorideHCID 27344145-Bromo-2-chloropyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 109543616'-Chloro-[2,3']bipyridinylYield 83.9%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
10 °C

Procedure

In a 300 mL inner volume flask replaced by nitrogen, tetrahydrofuran solution of isopropylmagnesium chloride (19.5% by weight, 30.3 g, 57.5 mmol) as a magnesiation reagent was charged, and cooled at 10° C., then tetrahydrofuran solution (20 g) of 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, then the reaction mixture was added dropwise to the solution of tetrahydrofuran (20 g) containing 2-bromopyridine (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, then reaction was stopped by adding saturated aqueous solution of ammonium chloride (50 g), and was left to stand to isolate organic layer. Organic layer was washed with saturated sodium chloride solution (10 g), then condensed under reduced pressure, to obtain crude 6-chloro-3,2′-bipyridine (10.6 g, purity: 81%, yield: 90%). The resultant crude 6-chloro-3,2′-bipyridine (10.6 g) was subjected to simple distillation under reduced pressure (0.9 mmHg, 124° C.), to obtain 6-chloro-3,2′-bipyridine (8.0 g, yield: 68%) as a 6-halogeno-3-arylpyridine derivative (III).

Workup

  1. additionwas charged
  2. additionAfter adding dropwise
  3. waitin the range of 10 to 20° C. for 2.0 hours
  4. additionAfter adding dropwise
  5. stirringthe reaction mixture was stirred in the range of 10 to 20° C. for 4.0 hours
  6. customreaction
  7. waitwas left
  8. customto isolate organic layer
  9. washOrganic layer was washed with saturated sodium chloride solution (10 g)
  10. customcondensed under reduced pressure
  11. customto obtain crude 6-chloro-3,2′-bipyridine (10.6 g, purity: 81%, yield: 90%)
  12. distillationThe resultant crude 6-chloro-3,2′-bipyridine (10.6 g) was subjected to simple distillation under reduced pressure (0.9 mmHg, 124° C.)

Sources & evidence

ORD record
ord-d748d9fce12d4d518251cf149236f651
Source dataset
uspto-grants-2014_06
Patent number
US08742127B2

Reaction notes

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