Hydrochloric Acid → N-(2-bromo-3-fluorophenyl)-2-(hydroxyimino)acetamide

HRID 1055834

Reaction equation

HRID 1055834 reaction equation
Cl.[NH2:2][OH:3].[O-]S([O-])(=O)=O.[Na+].[Na+].ClC(Cl)(Cl)C([O:15][CH2:16][CH3:17])O.[Br:20][C:21]1[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:22]=1[NH2:23].Cl.NC1C=CC=CC=1>O.CCO>[Br:20][C:21]1[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:22]=1[NH:23][C:16](=[O:15])[CH:17]=[N:2][OH:3]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 10587Chloral alcoholate2×HCID 24436Sodium SulfateHCID 443297Hydroxyamine hydrochlorideHCID 147700052-Bromo-3-fluoroaniline

Product 1

HCID 89781881N-(2-bromo-3-fluorophenyl)-2-(hydroxyimino)acetamideYield 87%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
40 °C

Procedure

Flask A: A 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, condenser, and temperature probe; the flask was charged with hydroxylamine hydrochloride (Fluka; 12.47 g, 179 mmol), Na2SO4 (51.7 g, 364 mmol), 2,2,2-trichloro-1-ethoxyethanol (15.78 g, 82 mmol), and water (240 ml). This was stirred to 40° C. to affect dissolution. Flask B: A mixture of 2-bromo-3-fluoroaniline (10.33 g, 54.4 mmol) in water (32.0 mL)/conc. HCl (14.95 mL, 179 mmol) was stirred at RT and then at 50° C. to attempt dissolution; EtOH (10 mL) was added as another attempt to dissolve the aniline to no avail. The fine slurry was added to Flask A containing the stirring 2,2,2-trichloro-1-ethoxyethanol solution at 40° C. The reaction was heated to 100° C. and was stirred for 1 h. The reaction was cooled to 5° C. in an ice bath, filtered through a disposable 0.45 micron ZapCap filter (very slow filtration), and washed with water to give N-(2-bromo-3-fluorophenyl)-2-(hydroxyimino)acetamide (12.34 g, 47.3 mmol, 87% yield) as a brown solid after it was dried in a vacuum oven. 1H NMR (400 MHz, CDCl3) δ ppm 6.92 (td, J=8.31, 1.37 Hz, 1H), 7.32 (td, J=8.31, 6.26 Hz, 1H), 7.60 (s, 1H), 7.87 (s, 1H), 8.25 (d, J=8.41 Hz, 1H), 8.98 (br. s., 1H). 19F NMR (377 MHz, CDCl3) δ ppm −104.01 (s, 1F). MS (ESI, pos. ion) m/z: 260.9/262.9 (M+1).

Workup

  1. customFlask A: A 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, condenser
  2. dissolutiondissolution
  3. customat 50° C.
  4. dissolutiondissolution
  5. temperatureThe reaction was heated to 100° C.
  6. stirringwas stirred for 1 h
  7. temperatureThe reaction was cooled to 5° C. in an ice bath
  8. filtrationfiltered through a disposable 0.45 micron ZapCap
  9. filtrationfilter (
  10. filtrationvery slow filtration), and
  11. washwashed with water

Sources & evidence

ORD record
ord-f39b2ac557d540fa9f7d3b67e0278b4b
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Linked notes

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