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

HRID 1803733Notes

Reaction equation

HRID 1803733 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) δ 7.30 (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-691881e05f214620b3134f1c7fafa95f
Source dataset
uspto-grants-2013_01
Patent number
US08350084B2

Reaction notes

Loading…