Tetrahydrofuran toluene → 1-(4-Chloro-pyridin-2-yl)-ethanone

HRID 658479Notes

Reaction equation

HRID 658479 reaction equation
C[Mg]Br.[C:4]1(C)C=CC=CC=1.C1COCC1.[Cl:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23](N(OC)C)=[O:24])[CH:18]=1>C1COCC1>[Cl:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23](=[O:24])[CH3:4])[CH:18]=1

Participants

5

Reactant 3

HCID 22635083Tetrahydrofuran tolueneHCID 535108144-chloro-N-methoxy-N-methylpyridine-2-carboxamideHCID 178418573HCID 178418573, compound

Product 1

HCID 130119861-(4-Chloro-pyridin-2-yl)-ethanoneYield 95.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 0° C. solution of 1.4 M methyl magnesium bromide in toluene/THF (6.89 mL, 9.65 mmol) in anhydrous THF (8.77 mL) was added a solution of 4-chloro-N-methoxy-N-methylpyridine-2-carboxamide (1.06 g, 5.26 mmol) in anhydrous THF (8.77 mL). The reaction mixture was stirred at RT under N2 for 17 h. The volatile solvent was removed under reduced pressure, and partitioned between EtOAc and water. The organic layer was washed with H2O, brine, dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by MPLC (biotage) eluted with 10% EtOAc/Hex to afford 652 mg of 1-(4-chloropyridin-2-yl)ethanone (95.5%) as a white crystalline solid. 1H-NMR (Acetone-d6) δ 8.69 (d, J=5.4 Hz, 1H), 7.95 (dd, J=2.1, 1.0 Hz, 1H), 7.71 (dd, J=5.4, 2.1 Hz, 1H), 2.65 (s, 3H); TLC (10% EtOAc/Hex), Rf=0.26.

Workup

  1. customThe volatile solvent was removed under reduced pressure
  2. custompartitioned between EtOAc and water
  3. washThe organic layer was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by MPLC (biotage)
  7. washeluted with 10% EtOAc/Hex

Sources & evidence

ORD record
ord-4709ca29dc10490ea2816eb1c89a1991
Source dataset
uspto-grants-2011_12
Patent number
US08076488B2

Reaction notes

Loading…