Dimethylformamide → 3-Fluoroisonicotinaldehyde

HRID 7159

Reaction equation

HRID 7159 reaction equation
CN(CCN(C)C)C.C([Li])CCC.[F:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.CN([CH:24]=[O:25])C>C1COCC1>[F:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[CH:24]=[O:25]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 677943-FluoropyridineHCID 178418339Butyllithium

Product 1

HCID 27630033-FluoroisonicotinaldehydeYield 37.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of TMEDA (389 uL, 2.58 mmol) in THF (10 mL) at −78° C. was added a solution of n-butyl lithium in THF (2.5M, 1.03 mL, 2.58 mmol). After 30 minutes at −78° C., 3-fluoropyridine (221 uL, 2.57 mmol) was added. After another 2 hours at −78° C., DMF (219 uL, 2.83 mmol) was added. After a further 2 hours at −78° C., the reaction was quenched with saturated aqueous NaHCO3 (20 mL), extracted with ether (4×15 mL), dried (Na2SO4), filtered and concentrated in vacuo to give the crude oil. Purification by column chromatography on silica gel (Hexanes: EtOAc 4:1) afforded the title compound as a pale yellow oil (120 mg, 37%). 1H NMR (CDCl3) 7.68 (t, 1H, J=5.2 Hz), 8.62 (d, 1H, J=4.7 Hz), 8.70 (s, 1H), 10.42 (s, 1H).

Workup

  1. waitAfter another 2 hours at −78° C.
  2. waitAfter a further 2 hours at −78° C.
  3. customthe reaction was quenched with saturated aqueous NaHCO3 (20 mL)
  4. extractionextracted with ether (4×15 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude oil
  9. customPurification by column chromatography on silica gel (Hexanes: EtOAc 4:1)

Sources & evidence

ORD record
ord-a94a42113b9747d29ec261a62954dea4
Source dataset
uspto-grants-2006_08
Patent number
US07084155B2

Linked notes

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