Hydrochloric Acid → 3-Chloro-4-(methylthio)phenylacetic acid

温度

80 °C

A reaction flask equipped with mechanical stirrer was charged with hydrazine hydrate (8.5 mL, 273 mmol). The hydrazine hydrate was cooled to −50° C. and then treated with (3-chloro-4-methylsulfanyl-phenyl)-oxo-acetic acid (12.6 g, 54.6 mmol) in one portion. An exotherm ensued that raised the temperature. The resulting white milky mixture was then heated to 80° C. After reaching 80° C., the heating element was removed, and the reaction mixture was then treated with potassium hydroxide (2.09 g, 31.7 mmol) in one portion. An exotherm was observed. The reaction was then stirred at 25° C. until the reaction temperature cooled back to 80° C. At this time, another portion of potassium hydroxide (2.09 g, 31.7 mmol) was added. Again, an exotherm was observed, and the resulting reaction mixture was allowed to cool back to 80° C. Once at 80° C., a third portion of potassium hydroxide (2.09 g, 31.7 mmol) was added to the reaction mixture. Another exotherm was observed, and after cooling back to 80° C., the fourth and final portion of potassium hydroxide (2.09 g, 31.7 mmol) was added. At this point, the heating element was added, and the reaction mixture was heated at 100° C. for 16 h. The resulting homogenous reaction mixture was cooled to 25° C. and then diluted with water (12 mL). The reaction mixture was then transferred to a separatory funnel, rinsing with additional water (12 mL) and diethyl ether (40 mL). The layers were separated, and the aqueous layer was transferred to a flask. The organic layer was extracted with water (2×15 mL) The aqueous layers were combined and treated with heptane (20 mL), and the resulting reaction mixture was vigorously stirred. This stirred solution was then treated dropwise with concentrated hydrochloric acid (26 mL) over 30 min while the temperature was kept under 50° C. with an ice bath. A cloudy suspension formed, and this suspension was stirred at 25° C. for 3 h. The solid that formed was collected by filtration and then washed sequentially with a 1N aqueous hydrochloric acid solution (2×6 mL), heptane (1×12 mL), and a solution of heptane/diethyl ether (15 mL, 4:1). The resulting solid was dried under high vacuum to afford (3-chloro-4-methylsulfanyl-phenyl)-acetic acid (10.48 g, 89%) as an off-white solid: mp 105.6-108.4° C.; EI-HRMS m/e calcd for C9H9ClO2S (M+) 216.0012. found 216.0022.

1. customA reaction flask equipped with mechanical stirrer
2. temperaturethat raised the temperature
3. customAfter reaching 80° C.
4. customthe heating element was removed
5. temperaturecooled back to 80° C
6. customthe resulting reaction mixture
7. temperatureto cool back to 80° C
8. temperatureafter cooling back to 80° C.
9. additionAt this point, the heating element was added
10. temperaturethe reaction mixture was heated at 100° C. for 16 h
11. temperatureThe resulting homogenous reaction mixture was cooled to 25° C.
12. customThe reaction mixture was then transferred to a separatory funnel
13. washrinsing with additional water (12 mL) and diethyl ether (40 mL)
14. customThe layers were separated
15. customthe aqueous layer was transferred to a flask
16. extractionThe organic layer was extracted with water (2×15 mL) The aqueous layers
17. additiontreated with heptane (20 mL)
18. customthe resulting reaction mixture
19. stirringwas vigorously stirred
20. customwas kept under 50° C. with an ice bath
21. customA cloudy suspension formed
22. stirringthis suspension was stirred at 25° C. for 3 h
23. customThe solid that formed
24. filtrationwas collected by filtration
25. washwashed sequentially with a 1N aqueous hydrochloric acid solution (2×6 mL), heptane (1×12 mL)
26. customThe resulting solid was dried under high vacuum

ORDレコード

ord-6c2ce382a445480cae10a37925715d9a

出典データセット

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07259166B2