4-Fluorobenzonitrile → 4-Fluoro-n-hydroxybenzimidamide

To a stirred solution of 4-fluorobenzonitrile (10 g, 82.5 mmol) in EtOH (71 mL) was added NH2OH.HCl (6.42 g, 92.1 mmol), followed by NaOH pellets (3.69 g, 92.1 mmol). The resulting reaction mixture was then heated at reflux for 3 h. The reaction progress was monitored by TLC using solvent system EtOAc:Hexane (1:1). After completion of reaction the solvent was evaporated under reduced pressure and the minimum amount of water (ca. 30 mL) was added to the residue. The mixture was extracted with dichloromethane (3×300 mL), dried over Na2SO4, and concentrated under vacuum. The crude compound obtained was recrystallized from hot toluene to obtain 8.0 g (63%) of 4-fluoro-N′-hydroxybenzimidamide as a colorless solid. 1H NMR (400 MHz, DMSO-d6): δ 9.6 (s, 1H), 7.07-7.67 (m, 2H), 7.18 (t, 2H, J=8.8 Hz), 5.80 (br s, 2H); LC-MS m/z calculated for [M+H]+ 155.05. found 155.1.

1. customThe resulting reaction mixture
2. temperaturewas then heated
3. temperatureat reflux for 3 h
4. customAfter completion of reaction the solvent
5. customwas evaporated under reduced pressure
6. additionthe minimum amount of water (ca. 30 mL) was added to the residue
7. extractionThe mixture was extracted with dichloromethane (3×300 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated under vacuum
10. customThe crude compound obtained
11. customwas recrystallized from hot toluene

ORD record

ord-cc33e830ea9347ceba74fbc560bad266

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266873B2