Tetrahydrofuran → 5-Bromo-2-cyclopropylpyridine

HRID 1441489Notes

Reaction equation

HRID 1441489 reaction equation
C1COCC1.[CH:6]1([Mg]Br)[CH2:8][CH2:7]1.Br[C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][N:13]=1.C(=O)(O)[O-].[Na+]>[Cl-].[Zn+2].[Cl-].Cl[Pd]Cl.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.[Fe+2]>[Br:18][C:15]1[CH:16]=[CH:17][C:12]([CH:6]2[CH2:7][CH2:8]2)=[N:13][CH:14]=1

Participants

8

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 693532,5-DibromopyridineHCID 516892Sodium BicarbonateHCID 178418630HCID 178418630, compound

Product 1

HCID 223177225-Bromo-2-cyclopropylpyridineYield 50%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 3007855ZincchlorideCatalyst

Procedure

0.5M Zinc chloride in THF (5.5 mL, 2.8 mmol) was added to a solution of 0.5M cyclopropylmagnesium bromide in THF (5.5 mL, 2.8 mmol) under argon. The solution was stirred at RT for 2 h at which time a slurry had formed. To this slurry was added in one portion 2,5-dibromopyridine (0.65 g, 2.8 mmol) and PdCl2×dppf (0.041 g, 0.050 mmol). After a few minutes an exotherm was seen and the slurry became thicker, the exotherm subsided and the slurry was stirred at RT overnight. The reaction mixture was poured into saturated sodium bicarbonate solution and extracted with ether. The ether phase was dried, filtered and concentrated, then re-dissolved in DCM and applied to a short plug of silica gel. The gel was washed with DCM and the washings were concentrated. The residue was taken up in ether and washed with 1.0M hydrochloric acid. The acidic water phase was made basic with 2.0M sodium hydroxide and the product was extracted back into ether. The combined ether phases were washed with brine, dried, filtered and concentrated to give 0.28 g (50%) of 5-bromo-2-cyclopropylpyridine as a yellow oil.

Workup

  1. customhad formed
  2. waitAfter a few minutes an exotherm was seen
  3. stirringthe slurry was stirred at RT overnight
  4. extractionextracted with ether
  5. dry with materialThe ether phase was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionre-dissolved in DCM
  9. washThe gel was washed with DCM
  10. concentrationthe washings were concentrated
  11. washwashed with 1.0M hydrochloric acid
  12. extractionthe product was extracted back into ether
  13. washThe combined ether phases were washed with brine
  14. customdried
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-1aa52efa1a4947a2882f743a4a691963
Source dataset
uspto-grants-2010_02
Patent number
US07655664B2

Reaction notes

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