Acetamide → N-{(4-Fluorophenyl)[(4-methylphenyl)sulfonyl]methyl}acetamide

HRID 1896666Notes

Reaction equation

HRID 1896666 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[C:10]([NH2:13])(=[O:12])[CH3:11].C[Si](Cl)(C)C.[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([OH:28])=[O:27])=[CH:22][CH:21]=1>C(#N)C.C1(C)C=CC=CC=1.COC(C)(C)C.O>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]([S:26]([C:23]2[CH:24]=[CH:25][C:20]([CH3:19])=[CH:21][CH:22]=2)(=[O:28])=[O:27])[NH:13][C:10](=[O:12])[CH3:11])=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 178Acetamide2×HCID 6397Chlorotrimethylsilane2×HCID 10818p-Toluenesulfinic acidHCID 680234-Fluorobenzaldehyde

Product 1

HCID 58235105N-{(4-Fluorophenyl)[(4-methylphenyl)sulfonyl]methyl}acetamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-fluorobenzaldehyde (3.18 g, 25.6 mmol), acetamide (3.78 g, 64.0 mmol) and trimethylsilyl chloride (3.58 mL, 28.2 mmol) in acetonitrile (12 mL) and toluene (12 mL) was heated at 50° C. for 1 hour. Additional acetamide (1.28 g, 21.7 mmol) and trimethylsilyl chloride (1.2 mL, 9.5 mmol) were added, and heating was continued for 90 minutes, at which point 4-methylbenzenesulfinic acid (6.00 g, 38.4 mmol) was added. The reaction was allowed to proceed at 50° C. for 18 hours, then was cooled to room temperature and diluted with tert-butyl methyl ether (20 mL). After 5 minutes of stirring, the mixture was further diluted with water (100 mL), cooled to 0° C. for 1 hour and filtered; the collected solid was rinsed with tert-butyl methyl ether. The product was obtained as a white solid. Yield: 4.276 g, 13.3 mmol, 52%. 1H NMR (400 MHz, DMSO-d6) δ 1.77 (s, 3H), 2.41 (s, 3H), 6.34 (d, J=10.5 Hz, 1H), 7.27 (dd, J=8.9, 8.9 Hz, 2H), 7.43 (d, J=8.0 Hz, 2H), 7.65 (dd, J=8.8, 5.5 Hz, 2H), 7.70 (d, J=8.3 Hz, 2H), 9.39 (d, J=10.5 Hz, 1H).

Workup

  1. temperatureheating
  2. additionwas added
  3. temperaturewas cooled to room temperature
  4. temperaturecooled to 0° C. for 1 hour
  5. filtrationfiltered
  6. washthe collected solid was rinsed with tert-butyl methyl ether
  7. customThe product was obtained as a white solid

Sources & evidence

ORD record
ord-7a0c55b863c84d3dbd6bc0e8d7e241d0
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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