Methyl iodide → 6-Bromo-3-methoxy-2-nitropyridine

HRID 1772883Notes

Reaction equation

HRID 1772883 reaction equation
O[C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.C[O-].[Na+].[Br:14]Br.[C:16]([O-:19])([O-])=O.[K+].[K+].IC>CO.CC(C)=O.C(O)(=O)C>[Br:14][C:5]1[N:4]=[C:3]([N+:8]([O-:10])=[O:9])[C:2]([O:19][CH3:16])=[CH:7][CH:6]=1

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 24408BromineHCID 270573-Hydroxy-2-nitropyridineHCID 10942334Sodium Methoxide

Product 1

HCID 226151626-Bromo-3-methoxy-2-nitropyridineYield 18.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 180AcetoneSolventHCID 887MethanolSolvent2×

Procedure

To a stirred solution of 3-hydroxy-2-nitropyridine (50.0 g, 0.34 mol) in MeOH (1 L) was added 30% NaOMe in MeOH (83 mL). The solution was stirred at rt for 30 min then cooled to 0° C. and Br2 (18 mL, 0.35 mol) was added dropwise maintaining this temperature. The reaction was then stirred at 0° C. for 2 h before the addition of glacial acetic acid (10 mL). Concentration in vacuo gave crude material (119 g), to which was added acetone (2 L) and K2CO3 (153 g, 0.8 mol) followed by iodomethane (85.5 mL, 1.4 mol). After stirring at 40° C. for 4 h the reaction was cooled to rt and filtered. After concentration of the filtrate in vacuo purification by flash chromatography eluting with 3:1 heptane-EtOAc yielded the title compound (14.4 g, 61.8 mmol).

Workup

  1. temperaturethen cooled to 0° C.
  2. temperaturemaintaining this temperature
  3. concentrationConcentration in vacuo
  4. customgave crude material (119 g)
  5. stirringAfter stirring at 40° C. for 4 h the reaction
  6. temperaturewas cooled to rt
  7. filtrationfiltered
  8. customAfter concentration of the filtrate in vacuo purification by flash chromatography
  9. washeluting with 3:1 heptane-EtOAc

Sources & evidence

ORD record
ord-d958290b3b584a6b909b6e3508418273
Source dataset
uspto-grants-2016_02
Patent number
US09249160B2

Reaction notes

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