Hydroxyamine hydrochloride → HCID 76816492, compound

To a mixture of 4-iodo-3-methylbenzonitrile (3.59 g, 14.8 mmol) and hydroxylamine hydrochloride (2.05 g, 29.5 mmol) in methanol (75 mL) under nitrogen was added sodium bicarbonate (4.96 g, 59.1 mmol). The reaction mixture was stirred at room temperature for 5 min. and then immersed in an oil bath and heated at reflux for 2 h. The heterogeneous mixture was filtered, the solid was washed with methanol, and the filtrate was concentrated under reduced pressure. The white solid residue was diluted with ethyl acetate (300 mL) but remained heterogeneous. The mixture was sonicated for 5 min and filtered under reduced pressure. By HPLC, the solid appeared to be inorganic. The filtrated was washed with (50 mL), and washed with a 10% aqueous solution of lithium chloride (50 mL), and washed with brine (50 mL). The combined aqueous layers were extracted with ethyl acetate (2×50 mL), and the combined organic layers were dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded N′-hydroxy-4-iodo-3-methylbenzimidamide (3.87 g, 14.0 mmol, 95% yield) as a white solid. The compound had an HPLC ret. time=0.993 min.−Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=276.8. 1H NMR (500 MHz, CDCl3) δ ppm 2.46 (s, 3H), 4.85 (br. s., 2H), 7.13 (dd, J=8.32, 2.22 Hz, 1H), 7.51 (d, J=1.66 Hz, 1H), and 7.84 (d, J=8.32 Hz, 1H).

1. customimmersed in an oil bath
2. temperatureheated
3. temperatureat reflux for 2 h
4. filtrationThe heterogeneous mixture was filtered
5. washthe solid was washed with methanol
6. concentrationthe filtrate was concentrated under reduced pressure
7. additionThe white solid residue was diluted with ethyl acetate (300 mL)
8. customThe mixture was sonicated for 5 min
9. filtrationfiltered under reduced pressure
10. washThe filtrated was washed with (50 mL)
11. washwashed with a 10% aqueous solution of lithium chloride (50 mL)
12. washwashed with brine (50 mL)
13. extractionThe combined aqueous layers were extracted with ethyl acetate (2×50 mL)
14. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
15. concentrationConcentration under reduced pressure

ORD record

ord-2b28bbbfc7c949b4937d8960df1d7d9b

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354398B2