Hydrochloric Acid → (Z)-4-amino-N-hydroxy-1,2,5-oxadiazole-3-carbonimidoyl chloride

Temperature

43.5 °C

4-Amino-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide (422 g, 2.95 mol) was added to a mixture of water (5.9 L), acetic acid (3 L) and 6 N hydrochloric acid (1.475 L, 3.0 equiv.) and the suspension was stirred at 42-45° C. until a clear solution was achieved. Sodium chloride (518 g, 3.0 equiv.) was added and this solution was stirred in an ice/water/methanol bath. A solution of sodium nitrite (199.5 g, 0.98 equiv.) in water (700 mL) was added over 3.5 h while maintaining the temperature below 0° C. After complete addition, stirring was continued in the ice bath for 1.5 h and then the reaction mixture was allowed to warm to 15° C. The precipitate was collected by filtration, washed well with water, taken in ethyl acetate (3.4 L), treated with anhydrous sodium sulfate (500 g) and stirred at room temperature for 1 h. This suspension was filtered through sodium sulfate (200 g) and the filtrate was concentrated on a rotary evaporator. The residue was dissolved in methyl tert-butyl ether (5.5 L), treated with the activated charcoal (40 g), stirred at room temperature for 40 min and filtered through Celite. The solvent was removed in a rotary evaporator and the resulting product was dried in a vacuum oven (45° C.) to give the desired product (256 g, 53.4%) as an off-white solid. 13C NMR (100 MHz, CD3OD) δ 155.8, 143.4, 129.7; C3H3ClN4O2 (MW 162.53), LCMS (EI) m/e 163/165 (M++H).

1. stirringthis solution was stirred in an ice/water/methanol bath
2. temperaturewhile maintaining the temperature below 0° C
3. additionAfter complete addition
4. stirringstirring
5. temperatureto warm to 15° C
6. filtrationThe precipitate was collected by filtration
7. washwashed well with water
8. additiontreated with anhydrous sodium sulfate (500 g)
9. stirringstirred at room temperature for 1 h
10. filtrationThis suspension was filtered through sodium sulfate (200 g)
11. concentrationthe filtrate was concentrated on a rotary evaporator
12. dissolutionThe residue was dissolved in methyl tert-butyl ether (5.5 L)
13. additiontreated with the activated charcoal (40 g)
14. stirringstirred at room temperature for 40 min
15. filtrationfiltered through Celite
16. customThe solvent was removed in a rotary evaporator
17. customthe resulting product was dried in a vacuum oven (45° C.)

ORD record

ord-ad0a72e676464911a07dbcafb87cba7d

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321755B2