ETHYL PYRUVATE-3-FORMYLAMINO-4-METHOXYPHENYLHYDRAZONE synthesis

Yield:107575-59-7 55.6%

Reaction Conditions:

Stage #1: N-(5-amino-2-methoxylphenyl)formamidewith hydrogenchloride in water at -20; for 0.5 h;
Stage #2: with sodium nitrite in ethanol;water at -15; for 0.833333 h;
Stage #3: 2-acetylpropanoic acid ethyl esterFurther stages;

Steps:

14 Example 14 Compound 3 was diazotized to react with HBF 4 to give Compound 4 and Compound 4 reacted with ethyl 2-methylacetoacetate 5

A three-neck flask containing 15 ml of 32% hydrochloric acid was stirred in an ice-ethanol bath.8g (0.048mol) of compound 3 is slowly added (about 15min), the temperature cannot exceed -20°C, the solution quickly becomes viscous,Add 5ml ethanol and stir for 30min. After 4.9 g of NaNO2 was dissolved in 7.4 ml of water (40% sodium nitrite solution) to form a solution,Slowly added to the three-necked flask, the reaction temperature does not exceed -15°C. After stirring for 20 minutes, add 25ml of cold ethanol and stir for 30min. Raise the temperature to -8°CThen 5.9 ml of 50% (0.062 mol) of HBF4 was added dropwise, the temperature did not exceed -3[deg.] C., 20 ml of ethanol was added, and the mixture was stirred at -5[deg.] C. for 30 min, and then the temperature was raised to 5[deg.] C.The golden yellow suspension was filtered and the cake was washed with 10 ml of cold ethanol to give compound 4.Then filter cake compound 4 was placed in 60ml cold ethanol and the temperature was controlled at -10°C.Add the cooled pre-formulated mixture, which has 6.8 g (0.047 mol) of ethyl 2-methylacetoacetate, 13 g (0.159 mol) of NaOAc and 40 ml of water,The temperature does not exceed -5°C when added dropwise. After the mixture was added dropwise, the yellow suspension was stirred at room temperature under nitrogen for 32 h.When the volume of the solution evaporates, it will be suction filtered.The filter cake was washed with 15 ml of 10% ethanol and 100 ml of ice water, and the filter cake was added to 15 ml of cold ethanol and filtered with suction.The material was dried in vacuo at 70° C. to give 7.45 g (0.0267 mol) of compound 5 in 55.6% yield (TLC: PE/EA=1:2).

References:

CN104557921,2018,B Location in patent:Paragraph 0097-0098