1009620-97-6

10489-74-4

79-04-9

1009620-97-6

To a suspension of ethyl 2-hydroxylamino-2-iminoacetate (1.17 g, 8.86 mmol) in chloroform (20 ml) cooled in an ice bath was slowly added pyridine (0.788 ml, 9.74 mmol), followed by the addition of chloroacetyl chloride (0.776 ml, 9.74 mmol) dropwise over a period of 5 min. After the dropwise addition, the reaction mixture was gradually warmed up to room temperature and stirred continuously for 1 hour. Upon completion of the reaction, the suspension was poured into a mixture of dichloromethane and water, the organic and aqueous phases were separated, and the aqueous phase was extracted with dichloromethane (note: this process produces a large amount of insoluble precipitate). The combined organic phases were washed sequentially with water and saturated saline, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting solid residue (about 900 mg) was dissolved in acetic acid (8 ml) and heated to reflux for 1 hour. At the end of the reaction, the hot reaction solution was poured into a mixture of ethyl acetate and saturated aqueous sodium carbonate to separate the organic phase. The organic phase was washed twice more with saturated aqueous sodium carbonate solution, followed by washing with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give ethyl 5-(chloromethyl)-1,2,4-diazole-3-carboxylate as a brown oil (0.29 g, 17% yield).