Formamide → N-((2,5-Difluorophenyl)(tosyl)methyl)formamide

HRID 1822754Notes

Reaction equation

HRID 1822754 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[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.C(OC)(C)(C)C.C(#N)C.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[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

9

Reactant 4

HCID 713FormamideHCID 6397ChlorotrimethylsilaneHCID 10818p-Toluenesulfinic acidHCID 1376632,5-Difluorobenzaldehyde

Product 1

HCID 22170178N-((2,5-Difluorophenyl)(tosyl)methyl)formamideYield 79.4%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
50 °C

Procedure

A 5 L three-necked round-bottomed flask, equipped with a mechanical stirrer, a condenser and a thermometer, was charged with 2,5-difluorobenzaldehyde (142.11 g, 1 mole). Toluene (500 ml), acetonitrile (500 ml), formamide (99.3 ml, 2.5 moles) and chlorotrimethylsilane (139.6 ml, 1.1 moles) were added respectively. The cloudy mixture was heated to 50° C. and stirred at this temperature for 7 hours. p-Toluenesulfinic acid (218.68 g, 1.4 moles) was added. The mixture was stirred at 50° C. for 6 hours and then 13 hours at room temperature. Methyl t-butyl ether (1.8 L) and water (1.7 L) were then added. The mixture was stirred at room temperature for 15 minutes at which time the organic layer was separated. The aqueous layer was extracted with methyl t-butyl ether (500 ml). Most of the solvents were removed from the combined organic extracts. To the residual white semi-solid, hexane (1 L) and water (1 L) were added. The slurry was stirred at room temperature for 30 minutes and filtered. The cake was washed with hexane (2×200 ml) and dried in a vacuum-oven (30° C.) for 18 hours. The product, N-[(2,5-Difluoro-phenyl)-(toluene-4-sulfonyl)-methyl]-formamide (258.3 g, yield 79%,), was obtained as a white powder.

Workup

  1. customA 5 L three-necked round-bottomed flask, equipped with a mechanical stirrer, a condenser
  2. stirringThe mixture was stirred at 50° C. for 6 hours
  3. custom13 hours
  4. customat room temperature
  5. stirringThe mixture was stirred at room temperature for 15 minutes at which time the organic layer
  6. customwas separated
  7. extractionThe aqueous layer was extracted with methyl t-butyl ether (500 ml)
  8. customMost of the solvents were removed from the combined organic extracts
  9. additionTo the residual white semi-solid, hexane (1 L) and water (1 L) were added
  10. stirringThe slurry was stirred at room temperature for 30 minutes
  11. filtrationfiltered
  12. washThe cake was washed with hexane (2×200 ml)
  13. customdried in a vacuum-oven (30° C.) for 18 hours

Sources & evidence

ORD record
ord-2cf5683ecdb041648e3568fee85e0bbd
Source dataset
uspto-grants-2006_05
Patent number
US07037923B2

Reaction notes

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