反应详情

温度

50 °C

Thionyl chloride (3.55 mL, 48.7 mmol) was added dropwise to a solution of 4-fluoro-3-methyl-benzoic acid (2.50 g, 16.2 mmol) in methanol (102 mL) at 0° C. The mixture was stirred at 50° C. for 2 hours. The reaction mixture was evaporated to dryness and the crude ester was then dissolved in N,N-dimethylformamide (10 mL). Sodium thiomethoxide (2.50 g, 35.7 mmol) was added and the reaction mixture was heated at 80° C. for 15 hours. The reaction mixture was then partitioned between 1M hydrochloric acid and ethyl acetate. The layers were separated and the organic layer was washed with 1M hydrochloric acid. The ethyl acetate layer was then dried over sodium sulfate, filtered, and evaporated to dryness. The resultant acid and ester mixture was suspended in acetic acid (20 mL). Hydrogen peroxide (5.0 mL of 30% w/w) was added and the reaction mixture was heated at 80° C. for 2 hours. The reaction mixture was diluted with water (20 mL) and the resulting mixture was extracted three times with 50 mL portions of ethyl acetate. The combined organics were evaporated to dryness and the residue was dissolved in tetrahydrofuran (10 mL). Water (10 mL) and lithium hydroxide (1.17 g, 48.7 mmol) were then added and the reaction mixture was heated at 65° C. for 4 hours. The reaction mixture was diluted with water (20 mL) and the resulting mixture was extracted three times with 20 mL portions of ethyl acetate. The aqueous layer was then made acidic with aqueous 6M hydrochloric acid and was extraced 3 times with 50 mL portions of ethyl acetate. The combined ethyl acetate extracts were dried over sodium sulfate, filtered, and evaporated to dryness to yield 3-methyl-4-methylsulfonyl-benzoic acid (2.25 g, 72%) as a white solid. ESI-MS m/z calc. 214.0, found 215.0 (M+1)+; Retention time: 0.97 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 13.48 (s, 1H), 8.07-7.94 (m, 3H), 3.27 (s, 3H), 2.70 (s, 3H).

1. customThe reaction mixture was evaporated to dryness
2. dissolutionthe crude ester was then dissolved in N,N-dimethylformamide (10 mL)
3. temperaturethe reaction mixture was heated at 80° C. for 15 hours
4. customThe reaction mixture was then partitioned between 1M hydrochloric acid and ethyl acetate
5. customThe layers were separated
6. washthe organic layer was washed with 1M hydrochloric acid
7. dry with materialThe ethyl acetate layer was then dried over sodium sulfate
8. filtrationfiltered
9. customevaporated to dryness
10. additionHydrogen peroxide (5.0 mL of 30% w/w) was added
11. temperaturethe reaction mixture was heated at 80° C. for 2 hours
12. additionThe reaction mixture was diluted with water (20 mL)
13. extractionthe resulting mixture was extracted three times with 50 mL portions of ethyl acetate
14. customThe combined organics were evaporated to dryness
15. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
16. temperaturethe reaction mixture was heated at 65° C. for 4 hours
17. extractionthe resulting mixture was extracted three times with 20 mL portions of ethyl acetate
18. dry with materialThe combined ethyl acetate extracts were dried over sodium sulfate
19. filtrationfiltered
20. customevaporated to dryness