Dimethylformamide → 3-Fluoroisonicotinaldehyde

HRID 1823270Notes

Reaction equation

HRID 1823270 reaction equation
C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.[F:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1.CN(C)[CH:30]=[O:31]>O1CCCC1.O>[F:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:27]=1[CH:30]=[O:31]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 677943-FluoropyridineHCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

Product 1

HCID 27630033-Fluoroisonicotinaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

Form a solution of lithium diisopropylamide by the addition of 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 0 to −10° C. under a nitrogen atmosphere. Stir for 30 min. Cool to −70° C. and add 3-fluoropyridine (4.29 mL, 0.05 mol) dropwise via syringe. Stir for 1 hour at this temperature. Add N,N-dimethylformamide (7.75 mL, 0.10 mol) dropwise via syringe and stir for 2 hours near −70° C. Add water (200 mL) when the mixture warms to −20° C. and extract with ethyl acetate. Dry the combined extracts over sodium sulfate and concentrate in vacuo. Elute the resulting residue over silica gel, allowing for isolation of the desired aldehyde (4.28 g, 68%) as an oil. MSEI): M+ 125.0 m/z.

Workup

  1. stirringStir for 1 hour at this temperature
  2. customwarms to −20° C.
  3. extractionextract with ethyl acetate
  4. dry with materialDry the combined extracts over sodium sulfate
  5. concentrationconcentrate in vacuo
  6. washElute the resulting residue over silica gel

Sources & evidence

ORD record
ord-b65542d58ba240508dd62734f4e51125
Source dataset
uspto-grants-2006_05
Patent number
US07037921B2

Reaction notes

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