反应详情

温度

95 °C

A mixture of 3.6 g (20 mmol) of 4-carboxybenzoic acid methyl ester, 25 mL of toluene and 6 mL of thionyl chloride was heated in an oil bath kept at ca. 90° C. Another 25 mL of toluene was added after 1 hr, an additional 6 mL quantity of thionyl chloride was added after 2.3 hr, and heating was continued for an additional 25 hr. The solvent and excess thionyl chloride were removed in vacuo. To the residue was added 25 mL of toluene and 6 mL of thionyl chloride and the mixture was again heated at 95° C. for 0.5 hr and then at 45° C. for 64 hr and finally at 90° C. for 3 hr. The solvent and excess thionyl chloride were again removed in vacuo. This crude acid chloride was mixed with 4.16 g (20 mmol) of 2-methoxybenzenepropanoic acid ethyl ester and 45 ml of methylene chloride. Aluminum chloride 10.7 g (80 mmol) was added in one portion and the resulting mixture was heated in an oil bath kept at 45° C. for 18 hr and then at 75° C. for 3.5 hr. After being cooled to room temperature, the mixture was poured onto crushed ice and 75 mL of 3N sulfuric acid solution was added. The resulting mixture was worked-up with ether in the usual manner. The residue was dissolved in 200 mL of ethanol. Concentrated sulfuric acid (5 mL) was added and the solution was heated under reflux for 5.8 hr. Most ethanol was removed under aspirator pressure and the residue was worked-up with ethyl acetate as usual. The crude product was purified by flash chromatography on 700 g of silica gel, eluting with 3:1 hexane-ethyl acetate, affording 2.0 g (27.1%) of the title compound as an off-white solid, mp 70°-71° C.

1. temperaturewas heated in an oil bath
2. customkept at ca. 90° C
3. temperatureheating
4. customThe solvent and excess thionyl chloride were removed in vacuo
5. additionTo the residue was added 25 mL of toluene and 6 mL of thionyl chloride
6. waitat 45° C. for 64 hr
7. waitfinally at 90° C. for 3 hr
8. customThe solvent and excess thionyl chloride were again removed in vacuo
9. temperaturethe resulting mixture was heated in an oil bath
10. waitkept at 45° C. for 18 hr
11. waitat 75° C. for 3.5 hr
12. temperatureAfter being cooled to room temperature
13. additionthe mixture was poured
14. additionwas added
15. temperaturethe solution was heated
16. temperatureunder reflux for 5.8 hr
17. customMost ethanol was removed under aspirator pressure
18. customThe crude product was purified by flash chromatography on 700 g of silica gel
19. washeluting with 3:1 hexane-ethyl acetate