Yield: 85.02%

Reaction Conditions:

with sodium ethanolate in ethanol for 6 h;Cooling with ice;

Steps:

1 Intermediate Intermediate V
Into a reaction flask equipped with a thermometer and a stirring device, add guanidine (5.90 g, 100 mmol),Ethanol and sodium ethoxide (17.00 g, 250 mmol), stir,Diethyl ethoxymethylene malonate (2.16 g, 100 mmol) was added dropwise under an ice water bath. After the addition, the reaction was reacted for 6 h. TLC showed that the reaction was complete. Add 30 mL of distilled water to the reaction solution to quench, and then add dropwise The 2M hydrochloric acid solution was brought to pH 6-7, stirred for 15 min, filtered, and dried at room temperature to obtain Intermediate V, 15.57 g of light brown solid, with a yield of 85.02%.

References:

Tianjin Medicine Institute;Zhi Shuang;Li Dongdong;Dai Linlin;Yang Zibo CN111559982, 2020, A Location in patent:Paragraph 0026