Dimethylformamide → 3,5-Dichloro-4-pyridinecarboxaldehyde

HRID 1823283Notes

Reaction equation

HRID 1823283 reaction equation
C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.Cl.[Cl:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([Cl:29])[CH:28]=1.CN(C)[CH:32]=[O:33]>O1CCCC1.O>[Cl:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([Cl:29])[C:28]=1[CH:32]=[O:33]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 22170150HCID 22170150, compoundHCID 178418339Butyllithium

Product 1

HCID 27629883,5-Dichloro-4-pyridinecarboxaldehydeYield 33.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

Form a solution of lithium diisopropylamide by the adding n-butyl lithium (37.5 mL, 0.06 mol, 1.6 M in hexanes) to diisopropylamine (8.40 mL, 0.06 mol) in tetrahydrofuran (200 mL) at −10 to−20° C. under a nitrogen atmosphere. Stir for 30 min., and cool to −60° C. Add 3,5-dichloropyridine hydrochloride (7.40 g, 0.05 mol) in small portions and stir for 1.5 hours at this temperature. Add N,N-dimethylformamide (7.75 mL, 0.10 mol) dropwise via syringe and stir for 1 hour near −60° C. Add water (200 mL) when the mixture is warmed near 0° C. and extract with ethyl acetate. Dry over sodium sulfate and concentrate in vacuo. Elute over silica gel with methanol/dichloromethane to give the desired aldehyde (2.94 g, 33%) as a light solid. MS(EI): Exact Mass Calc'd for: C6H3NOCl2 176.9562 m/z. Found: 176.9582 m/z.

Workup

  1. custom20° C.
  2. extractionextract with ethyl acetate
  3. dry with materialDry over sodium sulfate
  4. concentrationconcentrate in vacuo
  5. washElute over silica gel with methanol/dichloromethane

Sources & evidence

ORD record
ord-858763cd151f42099a81b10e577174fe
Source dataset
uspto-grants-2006_05
Patent number
US07037921B2

Reaction notes

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