Acetohydrazide → 5-methyl-3-phenyl-1H-1,2,4-triazole

To a suspension of ethyl benzimidate hydrochloride (2.0 g, 10.8 mmol) in EtOH (10 mL) was added sodium ethoxide (3.49 g, 4 mL, 10.8 mmol) at RT. The precipitated NaCl was filtrated off and washed with EtOH (14 mL). The filtrate was charged with acetohydrazide (880 mg, 11.9 mmol) and stirred at RT for 6 d. The crude reaction mixture was concentrated in vacuo. The crude product was suspended in NaOH (1M aqueous solution, 50 mL) and extracted with tert-butyl methyl ether (100 mL). The organic layer was washed with water (50 mL) and the aqueous layers were back-extracted with tert-butyl methyl ether (50 mL). After addition of dry ice to adjust the pH to 7, the organic layer appeared to contain almost no product and was discarded. The aqueous layer was adjusted to pH=7 by addition of HCl (25% aqueous solution) and extracted with dichloromethane (6×50 mL). The combined organic layer was dried over MgSO4 and concentrated in vacuo. The product was obtained after purification by flash chromatography (using silica gel and an ethyl acetate/hexane gradient) as white solid (154 mg, 9%).

1. filtrationThe precipitated NaCl was filtrated off
2. washwashed with EtOH (14 mL)
3. customThe crude reaction mixture
4. concentrationwas concentrated in vacuo
5. extractionextracted with tert-butyl methyl ether (100 mL)
6. washThe organic layer was washed with water (50 mL)
7. extractionthe aqueous layers were back-extracted with tert-butyl methyl ether (50 mL)
8. additionAfter addition of dry ice
9. additionThe aqueous layer was adjusted to pH=7 by addition of HCl (25% aqueous solution)
10. extractionextracted with dichloromethane (6×50 mL)
11. dry with materialThe combined organic layer was dried over MgSO4
12. concentrationconcentrated in vacuo
13. customThe product was obtained
14. customafter purification by flash chromatography (

ORD record

ord-52ca24f111a14d3eb55e087045d4c92e

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772510B2