Formamide → N-((2,4-Difluorophenyl)(tosyl)methyl)formamide

HRID 854433Notes

Reaction equation

HRID 854433 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH:11]([NH2:13])=[O:12].Cl[Si](C)(C)C.[C:19]1([CH3:28])[CH:24]=[CH:23][C:22]([S:25]([OH:27])=[O:26])=[CH:21][CH:20]=1>O.CCCCCC.CC(OC)(C)C.C(#N)C.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]([S:25]([C:22]1[CH:23]=[CH:24][C:19]([CH3:28])=[CH:20][CH:21]=1)(=[O:27])=[O:26])[NH:13][CH:11]=[O:12]

Participants

10

Reactant 4

HCID 713FormamideHCID 6397ChlorotrimethylsilaneHCID 10818p-Toluenesulfinic acidHCID 737702,4-Difluorobenzaldehyde

Product 1

HCID 22236872N-((2,4-Difluorophenyl)(tosyl)methyl)formamide

Reagents, catalysts & solvents 5

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 8058HexaneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

To 2,4-difluorobenzaldehyde (1.42 g, 10.0 mmol) is added toluene (5.0 mL), acetonitrile (5.0 mL), formamide (0.993 mL, 25.0 mmol) and chlorotrimethylsilane (1.40 mL, 11.0 mmol) in order. The cloudy mixture is heated to 50° C. and stirred at this temperature for 7 hours. p-Toluenesulfinic acid (2.19 g, 14.0 mmol) is added, and the mixture stirred at 50° C. for 6 hours, then for 3 hours at room temperature. MTBE (18.0 mL) and water (17.0 mL) are added, and the mixture stirred at room temperature for 15 minutes. The layers are separated, and the aqueous layer extracted with MTBE (5.0 mL). Most of the solvents are removed from the combined organic extracts leaving a white semi-solid. To the residual is added hexane (10.0 mL) and water (10.0 mL), and the resulting slurry stirred at room temperature for 30 minutes, then filtered. The cake is washed with hexane (2×) and dried in a vacuum-oven (30° C.) for 18 hours. The title compound may be obtained as a white powder (2.58 g, 79%).

Workup

  1. stirringthe mixture stirred at 50° C. for 6 hours
  2. waitfor 3 hours at room temperature
  3. stirringthe mixture stirred at room temperature for 15 minutes
  4. customThe layers are separated
  5. extractionthe aqueous layer extracted with MTBE (5.0 mL)
  6. customMost of the solvents are removed from the combined organic extracts
  7. customleaving a white semi-solid
  8. stirringthe resulting slurry stirred at room temperature for 30 minutes
  9. filtrationfiltered
  10. washThe cake is washed with hexane (2×)
  11. customdried in a vacuum-oven (30° C.) for 18 hours

Sources & evidence

ORD record
ord-65325c6b8ae64d94ac5499b682789c9c
Source dataset
uspto-grants-2007_08
Patent number
US07259171B2

Reaction notes

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