2-Fluoropyridine → (2-Fluoro-3-pyridinyl)phenylmethanone

HRID 347902Notes

Reaction equation

HRID 347902 reaction equation
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.CON(C)[C:19](=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[C:19]([C:15]1[C:10]([F:9])=[N:11][CH:12]=[CH:13][CH:14]=1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 97462-FluoropyridineHCID 569575N-Methoxy-N-methylbenzamideHCID 2724682Lithium diisopropylamide

Product 1

HCID 12711123(2-Fluoro-3-pyridinyl)phenylmethanoneYield 26.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a freshly prepared solution of lithium diisopropylamide (22 mmol) in dry THF (20 mL) under nitrogen and cooled to −78° was added a solution of 2-fluoropyridine (1.94 g, 20 mmol) in dry THF (10 mL). The reaction was stirred for 2.5 h at −78° before adding a solution of N-methoxy-N-methyl benzamide (3.47 g, 21 mmol) in THF (8 mL). The reaction mixture was allowed to warm to room temperature over 1.5 h and stir at room temperature for 1 h. The reaction was quenched with water (50 mL), extracted with EtOAc (2×50 mL), the extracts dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (5–20% EtOAc in isohexane) to give the title compound as a colourless oil (1.05 g, 26%). δH (CDCl3) 8.44 (1H, ddd, J 4.9, 2.0, 1.1 Hz), 8.06 (1H, ddd, J 9.3, 7.4, 2.0 Hz), 7.84 (2H, dm, J 8.4 Hz), 7.66 (1H, tt, J 7.4, 1.3 Hz), 7.52 (2H, tm, J 7.8 Hz), 7.38 (1H, ddd, J 6.8, 4.9, 1.9 Hz). LCMS (ES+) RT 3.27 minutes, 202 (M+H)+

Workup

  1. stirringstir at room temperature for 1 h
  2. customThe reaction was quenched with water (50 mL)
  3. extractionextracted with EtOAc (2×50 mL)
  4. dry with materialthe extracts dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography on silica (5–20% EtOAc in isohexane)

Sources & evidence

ORD record
ord-312a895d6994499dbf78b432149c4223
Source dataset
uspto-grants-2007_02
Patent number
US07176215B2

Reaction notes

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