Ethanol → 3-Fluoro-N-hydroxy-4-methylbenzamidine

HRID 660260Notes

Reaction equation

HRID 660260 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[C:5]#[N:6].C(O)C.[NH2:14][OH:15]>O>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[C:5](=[N:14][OH:15])[NH2:6]

Participants

5

Reactant 3

HCID 702EthanolHCID 787HydroxylamineHCID 5851403-Fluoro-4-methylbenzonitrile

Product 1

HCID 27373753-Fluoro-N-hydroxy-4-methylbenzamidineYield 91.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a suitable vessel equipped with mechanical stirrer under N2 atmosphere was charged 202.0 g of 3-fluoro-4-methylbenzonitrile followed by 1.0 L of ethanol. Hydroxylamine (144 mL of 50% solution in water) was added via addition funnel over 20 minutes. The mixture was stirred at ambient temperature until HPLC analysis showed that reaction was complete (no starting material remained). Water (3.0 L) was added dropwise to the pale yellow solution over 1 hour to give a thick slurry. The slurry was cooled in an ice water bath to 2° C. for 1.5 hours, filtered and dried under vacuum at 35° C. for 22 hours to give the title compound (230.3 g, 91.6%) as a white solid. 1H-NMR (CDCl3, 500 MHz) 67.30 (m, 2H), 7.19 (m, 1H), 4.87 (s, 2H), 2.28 (s, 3H); 13C-NMR (CDCl3, 500 MHz) δ162.15, 160.19, 151.58, 131.82, 131.76, 131.66, 131.62, 127.01, 126.87, 121.06, 112.69, 112.51, 14.48; 19F-NMR (CDCl3, 500 MHz) δ−116.35, −116.37, −116.39. LC-MS M+H169.19.

Workup

  1. customTo a suitable vessel equipped with mechanical stirrer under N2 atmosphere
  2. customshowed that reaction
  3. customto give a thick slurry
  4. temperatureThe slurry was cooled in an ice water bath to 2° C. for 1.5 hours
  5. filtrationfiltered
  6. customdried under vacuum at 35° C. for 22 hours

Sources & evidence

ORD record
ord-cb25657a3e2c43dbb9b26986a88b30f9
Source dataset
uspto-grants-2011_12
Patent number
US08084477B2

Reaction notes

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