Methyl formate → 2,3,5-Trichloropyridine-4-carbaldehyde

HRID 1977434Notes

Reaction equation

HRID 1977434 reaction equation
C([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[C:15]([Cl:16])=[CH:14][C:13]([Cl:17])=[CH:12][N:11]=1.[CH:18](OC)=[O:19].C([O-])(O)=O.[Na+]>C1COCC1>[Cl:9][C:10]1[C:15]([Cl:16])=[C:14]([CH:18]=[O:19])[C:13]([Cl:17])=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 7865Methyl formateHCID 27666Pyridine, 2,3,5-trichloro-HCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamide

Product 1

HCID 27629792,3,5-Trichloropyridine-4-carbaldehydeYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of lithium diisopropylamide (7.3 mL, 1.5 M in cyclohexane, 11 mmol) in 10 mL of dry THF under nitrogen at −78° C. was treated with 2,3,5-trichloropyridine (2 g, 11 mmol) in 20 mL THF over a 30 minute period, stirred an additional 30 minutes, then methyl formate (1.4 mL, 1.3 g, 22 mmol) in 14 mL THF was added slowly to the brown solution over 15 minutes, allowed to slowly warm to room temperature and stirred overnight. The resultant dark brown solution was poured onto ice and saturated NaHCO3, extracted with ethyl acetate, washed with brine, dried (Na2SO4) and concentrated. The brown oil was flash chromatographed on silica gel with 20-33% ethyl acetate/hexane to provide the title compound (1.7 g, 74%).

Workup

  1. stirringstirred overnight
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customchromatographed on silica gel with 20-33% ethyl acetate/hexane

Sources & evidence

ORD record
ord-1f1b856632844fffb09e8198cf0d1fd7
Source dataset
uspto-grants-2001_05
Patent number
US06232320B1

Reaction notes

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