反应详情

A cooled (0°) suspension of 60% sodium hydride/oil dispersion (7.2 g, 180 mmol) in anhydrous N,N-dimethylformamide (200 mL) under nitrogen was treated in portions with 4-amino-5-chloro-2-hydroxybenzoic acid, methyl ester (30.24 g, 150 mmol) so as to keep the pot temperature below 20° C. After one hour at 40° C., the mixture was treated with benzyl bromide (30.8 g, 180 mmol) and heated to 100°±5° C. for one hour, then cooled to room temperature and added to water (600 mL). The aqueous solution was extracted with methylene chloride (3×250 mL), and the combined organic solution was dried (Na2SO4), concentrated in vacuo, and filtered through a short column of alumina (eluted with methylene chloride). The filtrate was concentrated in vacuo, taken up in a mixture of 50% sodium hydroxide (50 mL), water (50 mL), and ethanol (100 mL), and refluxed for one hour. Most of the ethanol was removed in vacuo and water (400 mL) was added to dissolve all solid. The aqueous solution was extracted with ether (100 mL), then with petroleum ethers (30° C.-60° C., 100 mL), cooled (0° C.), and acidified to pH 3 with concentrated hydrochloric acid (about 90 mL). The resultant precipitate was filtered and the solid was washed with water, air dried, and recrystallized (2 crops) from ethanol to afford 25.51 g (61%) of tan crystals; mp 182°-184° C.

1. temperatureA cooled
2. customthe pot temperature below 20° C
3. temperatureheated to 100°±5° C. for one hour
4. extractionThe aqueous solution was extracted with methylene chloride (3×250 mL)
5. dry with materialthe combined organic solution was dried (Na2SO4)
6. concentrationconcentrated in vacuo
7. filtrationfiltered through a short column of alumina (eluted with methylene chloride)
8. concentrationThe filtrate was concentrated in vacuo
9. additiontaken up in a mixture of 50% sodium hydroxide (50 mL), water (50 mL), and ethanol (100 mL)
10. temperaturerefluxed for one hour
11. customMost of the ethanol was removed in vacuo and water (400 mL)
12. additionwas added
13. dissolutionto dissolve all solid
14. extractionThe aqueous solution was extracted with ether (100 mL)
15. temperaturewith petroleum ethers (30° C.-60° C., 100 mL), cooled (0° C.)
16. filtrationThe resultant precipitate was filtered
17. washthe solid was washed with water, air
18. customdried
19. customrecrystallized (2 crops) from ethanol