Pyridine → 3-Bromo-5-(bromomethyl)pyridine

HRID 1612946Notes

Reaction equation

HRID 1612946 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8]O)[CH:5]=[N:6][CH:7]=1.N1C=CC=CC=1.S(Cl)(C)(=O)=O.C([O-])([O-])=O.[K+].[K+].[Li+].[Br-:28]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][Br:28])[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 82050Lithium BromideHCID 2784733(5-Bromo-3-pyridinyl)methanol

Product 1

HCID 149329483-Bromo-5-(bromomethyl)pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-bromo-3-pyridylmethanol [see Kauffman, T., and Fischer, H.(1973) Chem. Ber. 106, 220-227.] (0.525 gms, 2.79 mmol) in methylene chloride (2.6 mls) at 0° C. is added pyridine (0.26 mls, 3.21 mmol) then mesyl chloride (0.25 mls, 3.23 mmol). After stirring 2 hours, K2CO3 (0.88 gms, 6.37 mmol) is added. Stirring is continued for one hour and the ice bath is removed. The mixture is diluted with methylene chloride and washed with saturated aqueous NaHCO3. The organic layer is dried over Na2SO4 and evaporated to a viscous residue (>0.6 gms). The residue is dissolved in methylene chloride (8.8 mls) and tetrahydrofuran (4.4 mls) without further purification or characterization. LiBr powder (0.46 gms, 5.53 mmol) is introduced and the reaction is immersed in an oil bath (80° C.) for one hour. The crude mixture is concentrated and resolvated with ethyl acetate. Any remaining residue is pulverized and rinsed with methylene chloride. Combined organics are dried over Na2SO4 and evaporated to a solid (0.7 gms, 2.79 mmol; 100%). 1H NMR (CDCl3, 300 MHz) δ8.65 (s, 1H), 8.55 (s, 1H), 7.90 (s, 1H), 4.45 (s, 2H).

Workup

  1. stirringStirring
  2. waitis continued for one hour
  3. customthe ice bath is removed
  4. additionThe mixture is diluted with methylene chloride
  5. washwashed with saturated aqueous NaHCO3
  6. dry with materialThe organic layer is dried over Na2SO4
  7. customevaporated to a viscous residue (>0.6 gms)
  8. dissolutionThe residue is dissolved in methylene chloride (8.8 mls)
  9. customtetrahydrofuran (4.4 mls) without further purification or characterization
  10. customthe reaction is immersed in an oil bath
  11. wait(80° C.) for one hour
  12. concentrationThe crude mixture is concentrated
  13. washrinsed with methylene chloride
  14. dry with materialCombined organics are dried over Na2SO4
  15. customevaporated to a solid (0.7 gms, 2.79 mmol; 100%)

Sources & evidence

ORD record
ord-c666608c2e7e492ebe741bd5f17a1866
Source dataset
uspto-grants-1993_03
Patent number
US05191084

Reaction notes

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