2,6-Lutidine → 1-(3-Methyl-3H-benzotriazol-5-yl)-2-(6-methyl-pyridin-2-yl)-ethanone

HRID 860101Notes

Reaction equation

HRID 860101 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1.C([Li])CCC.CON(C)[C:17]([C:19]1[CH:28]=[CH:27][C:22]2[N:23]=[N:24][N:25]([CH3:26])[C:21]=2[CH:20]=1)=[O:18]>O1CCCC1>[CH3:26][N:25]1[C:21]2[CH:20]=[C:19]([C:17](=[O:18])[CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=3)[CH:28]=[CH:27][C:22]=2[N:23]=[N:24]1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 859571723-methyl-3H-benzotriazole-5-carboxylic acid methoxy-methyl-amideHCID 178418339Butyllithium

Product 1

HCID 688986501-(3-Methyl-3H-benzotriazol-5-yl)-2-(6-methyl-pyridin-2-yl)-ethanoneYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

A solution of 2,6-dimethylpyridine (292 μl, 2.5 mmol) in 10 ml anhydrous tetrahydrofuran was cooled to −30° C. A 2.5M solution of n-butyllithium in hexanes (1.0 ml, 2.5 mmol) was slowly added dropwise. Once the addition was complete, the reaction was stirred at −30° C. for 1 hour. In a separate flask, a solution of 3-methyl-3H-benzotriazole-5-carboxylic acid methoxy-methyl-amide (500 mg, 2.27 mmol) in 3 ml anhydrous tetrahydrofuran was cooled to −30° C. The cold anion solution was slowly added dropwise to the cold amide solution. Once the addition was complete, the reaction was allowed to slowly warm to room temperature over several hours and stirred overnight. The reaction was quenched with water and the solvent removed by rotary evaporation. The residue was dissolved in saturated aqueous ammonium chloride and extracted three times with chloroform. The combined organics were washed once with water and then once with brine. The combined organics were dried over sodium sulfate, filtered and concentrated to dryness. Crude material was purified on Biotage Flash 40S silica gel column using hexanes/ethyl acetate gradient system (80:20 to 40:60, respectively) as eluent to afford 1-(3-Methyl-3H-benzotriazol-5-yl)-2-(6-methyl-pyridin-2-yl)-ethanone (320 mg, 53%).

Workup

  1. additionOnce the addition
  2. additionOnce the addition
  3. temperatureto slowly warm to room temperature over several hours
  4. stirringstirred overnight
  5. customThe reaction was quenched with water
  6. customthe solvent removed by rotary evaporation
  7. dissolutionThe residue was dissolved in saturated aqueous ammonium chloride
  8. extractionextracted three times with chloroform
  9. washThe combined organics were washed once with water
  10. dry with materialThe combined organics were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness
  13. customCrude material was purified on Biotage Flash 40S silica gel column

Sources & evidence

ORD record
ord-0d0a6403091d422ca36a814b93612157
Source dataset
uspto-grants-2006_12
Patent number
US07153872B2

Reaction notes

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