Synthetic method for repaglinide

[0017] A kind of synthetic method of repaglinide, the concrete steps of this method are as follows:

[0018] S1: add 50 g of magnesium scraps and 2 g of iodine to 200 ml of tetrahydrofuran solution, add 15 g of isobutyl bromide at 20°C under nitrogen flow, and stir to react to obtain a reaction solution. The temperature of ℃, and the time of stirring reaction is 15min;

[0019] S2: Heat the toluene solution to 10°C, add the mixed solution, stir at the same temperature for 3 hours, stand for stratification, wash the organic layer with saturated sodium bicarbonate and water, and evaporate the solvent under reduced pressure to obtain a colorless liquid. The mixed solution It is a mixture of concentrated hydrochloric acid and ice water;

[0020] S3: mixing the reaction solution in step S1 into the colorless liquid, stirring at room temperature, then adding methanol 60ml and sodium hydroxide 2g, heating up and stirring, the temperature of heating and stirring is 50 ℃, and the stir...

[0024] A kind of synthetic method of repaglinide, the concrete steps of this method are as follows:

[0025] S1: add 70 g of magnesium scraps and 4 g of iodine to 300 ml of tetrahydrofuran solution, add 20 g of isobutyl bromide at 30°C under nitrogen flow, and stir to react to obtain a reaction solution, which is placed for later use. During the stirring reaction, keep 30 g The temperature of ℃, and the time of stirring reaction is 20min;

[0026] S2: Heat the toluene solution to 20°C, add the mixed solution, stir at the same temperature for 4 hours, stand for stratification, wash the organic layer with saturated sodium bicarbonate and water, and evaporate the solvent under reduced pressure to obtain a colorless liquid. The mixed solution It is a mixture of concentrated hydrochloric acid and ice water;

[0027] S3: mix the reaction solution in step S1 into the colorless liquid, stir at room temperature, then add 80 ml of methanol and 4 g of sodium hydroxide, heat up and stir ...

[0031] A kind of synthetic method of repaglinide, the concrete steps of this method are as follows:

[0032] S1: add 60 g of magnesium scraps and 3 g of iodine to 260 ml of tetrahydrofuran solution, add 18 g of isobutyl bromide at 25°C under nitrogen flow, and stir to react to obtain a reaction solution, which is placed for later use. During the stirring reaction, keep 25 The temperature of ℃, and the time of stirring reaction is 18min;

[0033] S2: heat the toluene solution to 15°C, add the mixed solution, stir at the same temperature for 3 hours, stand for stratification, wash the organic layer with saturated sodium bicarbonate and water, and evaporate the solvent under reduced pressure to obtain a colorless liquid. The mixed solution It is a mixture of concentrated hydrochloric acid and ice water;

[0034] S3: mixing the reaction solution in step S1 into the colorless liquid, stirring at room temperature, then adding 70 ml of methanol and 3 g of sodium hydroxide, heating u...