Methyl iodide → 2-(2-Chloro-4-methoxy-phenyl)-1-(5-methyl-pyrazin-2-yl)-propan-1-one

HRID 1097856Notes

Reaction equation

HRID 1097856 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH2:10][C:11]([C:13]1[CH:18]=[N:17][C:16]([CH3:19])=[CH:15][N:14]=1)=[O:12].[H-].[Na+].[CH3:22]I>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:22])[C:11]([C:13]1[CH:18]=[N:17][C:16]([CH3:19])=[CH:15][N:14]=1)=[O:12]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 666991242-(2-Chloro-4-methoxy-phenyl)-1-(5-methyl-pyrazin-2-yl)-ethanone

Product 1

HCID 666991162-(2-Chloro-4-methoxy-phenyl)-1-(5-methyl-pyrazin-2-yl)-propan-1-oneYield 76.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(2-chloro-4-methoxy-phenyl)-1-(5-methyl-pyrazin-2-yl)-ethanone (370 mg, 1.3 mmol) in DMF (5 mL) was added slowly over 30 min to a suspension of NaH (50% in mineral oil, 96 mg, 1.9 mmol) in DMF (2 mL). After 30 min, methyl iodide (199 mg, 1.4 mmol) was added slowly, and the mixture was stirred for 2 d at r.t. The reaction mixture was taken up in ethyl acetate, and washed (water, brine). The organic layer was separated, dried (Na2SO4), and the solvent was evaporated to give a residue, which was purified by column chromatography (silica gel, heptane:ethyl acetate=100:0-80:20) to give the title compound (290 mg, 75%). 1H NMR (300 MHz, CDCl3) □ 9.08 (1H, s), 8.45 (1H, s), 7.11 (1H, d), 6.92 (1H, d), 6.73 (1H, dd), 5.53 (1H, q), 3.75 (3H, s), 2.61 (3H, s), 1.49 (3H, d); MS (m/e)=291.0 [MH+].

Workup

  1. washwashed (water, brine)
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. customthe solvent was evaporated
  5. customto give a residue, which
  6. customwas purified by column chromatography (silica gel, heptane:ethyl acetate=100:0-80:20)

Sources & evidence

ORD record
ord-88ecbd6ce4e04a6d90ac36f71d74fd38
Source dataset
uspto-grants-2012_03
Patent number
US08143280B2

Reaction notes

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