Methyl iodide → 4-Fluoro-N-methyl-N-[2-(5-methyl-furan-2-yl)-ethyl]-benzamide

HRID 2110432Notes

Reaction equation

HRID 2110432 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:20]=[CH:19][C:7]([C:8]([NH:10][CH2:11][CH2:12][C:13]2[O:14][C:15]([CH3:18])=[CH:16][CH:17]=2)=[O:9])=[CH:6][CH:5]=1.I[CH3:22]>C1COCC1>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([N:10]([CH3:22])[CH2:11][CH2:12][C:13]2[O:14][C:15]([CH3:18])=[CH:16][CH:17]=2)=[O:9])=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 218748464-Fluoro-N-[2-(5-methyl-2-furanyl)ethyl]benzamide

Product 1

HCID 218749624-Fluoro-N-methyl-N-[2-(5-methyl-furan-2-yl)-ethyl]-benzamideYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (60% dispersion in oil, 65 mg, 1.63 mmol) was added portionwise to a solution of 4-fluoro-N-[2-(5-methyl-2-furanyl)ethyl]benzamide (269 mg, 1.09 mmol, 237A) in THF (5 mL). After gas evolution ceased, iodomethane (0.14 mL, 2.18 mmol) was added drop-wise. Once HPLC analysis showed the reaction to be 50% complete, the mixture was concentrated under reduced pressure and resubjected to the above conditions. After all the starting material was consumed, H2O was added and the resulting mixture was extracted with EtOAc (2×5 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography on silica gel eluting with 20% acetone/CHCl3 gave 238 mg (84%) of compound 425A. HPLC: 98% at 2.94 min (retention time) (Phenomenex-prime S5-C 18 column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z [M+H]=262.38.

Workup

  1. customthe reaction
  2. concentrationthe mixture was concentrated under reduced pressure
  3. customAfter all the starting material was consumed
  4. additionH2O was added
  5. extractionthe resulting mixture was extracted with EtOAc (2×5 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography on silica gel eluting with 20% acetone/CHCl3

Sources & evidence

ORD record
ord-836ff9d6fa49421690d6601f3dd0c860
Source dataset
uspto-grants-2009_04
Patent number
US07517904B2

Reaction notes

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