Background and overview[1][2]
3-Aminobenzaldehyde ethylene glycol acetal can be used as a pharmaceutical synthesis intermediate.
Preparation[1]
3-Aminobenzaldehyde ethylene glycol acetal is prepared as follows:
1) Synthesis of compound 16b: Dissolve compound 16a (5g, 33.1mmol) in 50mL dry toluene, add ethylene glycol (22.1mL, 364mL) and p-toluenesulfonic acid (570mg, 3.31mmol), and place The reaction was carried out under reflux at 110°C overnight (about 12 hours). After TLC detected that the reaction was complete, the reaction solution was cooled to room temperature, washed three times with 70 mL of saturated NaHCO3 solution, washed with saturated brine, dried over anhydrous sodium sulfate, and spun to dryness to obtain 7 g. Compound 16b was a viscous liquid in quantitative yield.
2) Synthesis of compound 16c (3-aminobenzaldehyde glycol acetal): Dissolve compound 16b (6.45g, 33.1mmol) in a mixed solvent of ethanol (50mL) and water (25mL) at room temperature. Add ammonium chloride (885.4mg, 16.55mmol) and iron powder (9.27g, 165.5mmol), place it at 80°C to react for about 30 minutes, and after TLC detects that the raw material reaction is complete, filter it while it is hot, and spin off the ethanol in the filtrate under reduced pressure. , extracted three times with 50 mL ethyl acetate, combined the organic phases, washed with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and the crude product was purified by column chromatography (PE:EA=6:1~4:1) to obtain yellow liquid compound 16c4 .52g, yield 82.7%.
Application
3-Aminobenzaldehyde ethylene glycol acetal can be used as a pharmaceutical synthesis intermediate, such as the following reaction:
Dissolve compound 3-aminobenzaldehyde glycol acetal in DMF (5mL) at room temperature, add K2CO3 (1.25g, 9.09mmol), and add ethyl bromoacetate (504.4uL, 4.55mmol) with slow stirring. It was added dropwise and the reaction was stirred at room temperature for 8 hours. After TLC detects that the raw material reaction is complete, add 20 mL of ethyl acetate to the reaction solution, wash three times with 20 mL of water, separate the liquids, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and the crude product is purified by column chromatography (PE:EA=3: 1) 625.9 mg of yellow liquid was obtained, with a yield of 82.3%.
Main reference materials
[1]CN201710229724.7 Indazole compounds and their use in preparing IDO inhibitor drugs
