Methyl iodide → 4-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]-1-methylpiperazin-2-one

HRID 389991Notes

Reaction equation

HRID 389991 reaction equation
[H-].[Na+].[CH2:3]([C:5]1[C:27]([F:28])=[CH:26][C:8]([O:9][C:10]2[CH:24]=[CH:23][C:13]([C:14]([N:16]3[CH2:21][CH2:20][NH:19][C:18](=[O:22])[CH2:17]3)=[O:15])=[CH:12][C:11]=2[F:25])=[C:7]([O:29][CH3:30])[CH:6]=1)[CH3:4].IC.[C:33](OCC)(=O)C>CN(C)C=O.O>[CH2:3]([C:5]1[C:27]([F:28])=[CH:26][C:8]([O:9][C:10]2[CH:24]=[CH:23][C:13]([C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:33])[C:18](=[O:22])[CH2:17]3)=[O:15])=[CH:12][C:11]=2[F:25])=[C:7]([O:29][CH3:30])[CH:6]=1)[CH3:4]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 671162484-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

Product 1

HCID 671162384-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]-1-methylpiperazin-2-oneYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in oil, 25 mg, 0.6 mmol) was added to a solution of 4-[4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoy]-piperazin-2-one (which may be prepared in accordance with the experimental described in Example 5, step 1; 200 mg, 0.5 mmol) in N,N-dimethylformamide (5 mL). The reaction mixture was stirred at room temperature for 15 minutes prior to the addition of iodomethane (0.48 mL, 0.77 mmol). After stirring at room temperature for 1 hour, the reaction mixture was diluted by addition of ethyl acetate (30 mL) and water (30 mL). The two phases were separated and the aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic phases were finally washed with a saturated solution of sodium chloride (5×20 mL), dried over sodium sulfate, filtered and concentrated under vacuum to afford the title product as a yellow oil (200 mg, 97%).

Workup

  1. custommay be prepared in accordance with the
  2. stirringAfter stirring at room temperature for 1 hour
  3. customThe two phases were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×30 mL)
  5. washThe combined organic phases were finally washed with a saturated solution of sodium chloride (5×20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-d5257bc648f84e18a20f56bac4361c3b
Source dataset
uspto-grants-2013_02
Patent number
US08383621B2

Reaction notes

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