Formamide → N-[(4-Fluorophenyl)((4-methylphenyl)sulfonyl)methyl]formamide

HRID 1379161Notes

Reaction equation

HRID 1379161 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH:10]([NH2:12])=[O:11].Cl[Si](C)(C)C.[C:18]1([CH3:27])[CH:23]=[CH:22][C:21]([S:24]([OH:26])=[O:25])=[CH:20][CH:19]=1>C(#N)C.C1(C)C=CC=CC=1.O.COC(C)(C)C.CO>[C:18]1([CH3:27])[CH:23]=[CH:22][C:21]([S:24]([CH:6]([NH:12][CH:10]=[O:11])[C:5]2[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=2)(=[O:26])=[O:25])=[CH:20][CH:19]=1

Participants

10

Reactant 4

HCID 713FormamideHCID 6397ChlorotrimethylsilaneHCID 10818p-Toluenesulfinic acidHCID 680234-Fluorobenzaldehyde

Product 1

HCID 10828539N-[(4-Fluorophenyl)((4-methylphenyl)sulfonyl)methyl]formamideYield 90%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 4-fluorobenzaldehyde (124 g, 979 mmoles) in acetonitrile (620 mL, 5 volumes) and toluene (620 mL, 5 volumes) was added formamide (110 g, 2.45 moles, 2.5 equiv.) followed by chlorotrimethylsilane (119 g, 1.07 moles, 1.1 equiv.). The reaction was heated at 50° C. under nitrogen for 5 hours. To the resulting white slurry was added p-toluenesulfinic acid (230 g, 1.47 moles, 1.5 equiv.) and the reaction was heated at 50° C. for an additional 5 hours then cooled to ambient temperature. Methanol (250 mL) and t-butyl methyl ether (620 mL) were added. After 15 minutes the reaction was poured into water (3L) pre-cooled to 0° C. After stirring for 30 minutes at 0° C., the product was collected by suction filtration and rinsed with t-butyl methyl ether (250 mL). The product, a white, crystalline solid, was dried to a constant weight at 40° C./<1 mm Hg to afford 270 g (879 mmoles) of desired product (90% yield). 1H NMR (300 MHz, CD3CN) δ 7.99 (1H, s), 7.92 (1H, m), 7.71 (2H, d, J=8.3 Hz), 7.49 (2H, dd, J=5.3, 8.8 Hz), 7.39 (2H, d, J=8.1 Hz), 7.16 (2H, t, J=8.8 Hz), 6.3I (1H, d, J=10.6 Hz), 2.42 (3H, s).

Workup

  1. temperaturethe reaction was heated at 50° C. for an additional 5 hours
  2. temperaturethen cooled to ambient temperature
  3. temperaturepre-cooled to 0° C
  4. filtrationthe product was collected by suction filtration
  5. washrinsed with t-butyl methyl ether (250 mL)
  6. customThe product, a white, crystalline solid, was dried to a constant weight at 40° C./<1 mm Hg

Sources & evidence

ORD record
ord-80d508db9cb0425c8bd997fb17ad6b05
Source dataset
uspto-grants-1997_09
Patent number
US05670527

Reaction notes

Loading…