Toluene → 3-Bromo-6-methoxypyridin-2-amine

HRID 1691836Notes

Reaction equation

HRID 1691836 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[Br:9].[CH3:10][Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.S(OC)(OC)(=O)=O>CN(C=O)C>[Br:9][C:3]1[C:2]([NH2:1])=[N:7][C:6]([O:8][CH3:10])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6497Dimethyl SulfateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 178508959HCID 178508959, compound

Product 1

HCID 234358793-Bromo-6-methoxypyridin-2-amineYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-amino-5-bromo-pyridin-2-ol (1.0 g) in DMF (30 mL) was added at 0° C. 0.5 M potassium bis(trimethylsilyl)amide in toluene (11.7 mL, 5.83 mmol) under Ar atmosphere. After stirring for 10 minutes, dimethyl sulfate (0.64 mL, 5.26 mmol) was added at 0° C. The mixture was allowed to warm to room temperature, and was stirred for an additional two hours. Buffer (pH 7) was added and mixture was extracted with diethyl ether. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to dryness. Purification of the residue by flash chromatography (hexane/toluene 45:55) gave pure 3-bromo-6-methoxy-pyridin-2-ylamine (260 mg, 13% overall).

Workup

  1. stirringwas stirred for an additional two hours
  2. additionBuffer (pH 7) was added
  3. extractionmixture was extracted with diethyl ether
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customPurification of the residue by flash chromatography (hexane/toluene 45:55)

Sources & evidence

ORD record
ord-ce2cadbc33ae4ac9b518f9027dcd802b
Source dataset
uspto-grants-2012_04
Patent number
US08153809B2

Reaction notes

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