Hydrochloric Acid → 3-Chloro-4-(methoxycarbonyl)benzoic acid

In a 2 L RB flask equipped with a magnetic stirrer, a slurry of crude 2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid methyl ester (Example 74; 32 g, 0.10 mol) in water (300 mL) was treated with 1N sodium hydroxide solution (300 mL, 0.3 mol). Most of the solids quickly dissolved and the solution was stirred at room temperature overnight. The mixture was filtered through Celite® to remove undissolved solids (residual N,N-dicyclohexylurea) and the filter cake was washed with water (2×30 mL). The combined filtrates were transferred to a separatory funnel and extracted with diethyl ether (2×300 mL). Each diethyl ether extract was back-washed in turn with brine (50 mL). The combined aqueous phases were stirred as they were acidified by the addition of 6N hydrochloric acid (55 mL, 0.33 mol). The resulting mixture was stirred overnight at room temperature, then the precipitated solids were collected by filtration and the filter cake was washed with water (2×60 mL). The slightly off-white solid was dried in vacuo over P2O5 then was dissolved in warm ethyl acetate (400 mL) and the solution was treated with charcoal (4 g) and filtered through a bed of Celite®. The filter cake was washed with ethyl acetate (2×40 mL). The combined filtrates were concentrated to about 250 mL then sufficient hexane was added to the hot stirred solution to produce a permanent cloud point. The mixture was cooled to room temperature, then was stored at −20° C. overnight. The solids were collected by filtration and were washed with hexane (2×50 mL) to give 2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid, mp 167-1690° C. (27.1 g, 88.6%) from 3-chloro-4-(methoxycarbonyl)benzoic acid].

1. customIn a 2 L RB flask equipped with a magnetic stirrer
2. dissolutionMost of the solids quickly dissolved
3. filtrationThe mixture was filtered through Celite®
4. customto remove undissolved solids (residual N,N-dicyclohexylurea)
5. washthe filter cake was washed with water (2×30 mL)
6. customThe combined filtrates were transferred to a separatory funnel
7. extractionextracted with diethyl ether (2×300 mL)
8. extractionEach diethyl ether extract
9. washwas back-washed in turn with brine (50 mL)
10. stirringThe combined aqueous phases were stirred as they
11. stirringThe resulting mixture was stirred overnight at room temperature
12. filtrationthe precipitated solids were collected by filtration
13. washthe filter cake was washed with water (2×60 mL)
14. dry with materialThe slightly off-white solid was dried in vacuo over P2O5
15. dissolutionthen was dissolved in warm ethyl acetate (400 mL)
16. additionthe solution was treated with charcoal (4 g)
17. filtrationfiltered through a bed of Celite®
18. washThe filter cake was washed with ethyl acetate (2×40 mL)
19. concentrationThe combined filtrates were concentrated to about 250 mL
20. additionsufficient hexane was added to the hot stirred solution
21. customto produce a permanent cloud point
22. temperatureThe mixture was cooled to room temperature
23. waitwas stored at −20° C. overnight
24. filtrationThe solids were collected by filtration
25. washwere washed with hexane (2×50 mL)

ORDレコード

ord-87afad61e4aa48aea01b76b648187a07

出典データセット

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06515124B2