Potassium Carbonate → HCID 5046240, compound

Temperature

-45 °C

Dimethylformamide (DMF), 100 ml, was poured into a 4 l indented 3 neck round bottom flask equipped with a nitrogen bubbler and an overhead stirrer (glass shaft, teflon Paddle). The hot 2-bromo-2-methylpropionic acid was then added to the flask through a powder funnel. The flask and the funnel were rinsed with 4×100 ml portions of DMF and were added to the reaction flask. A thermometer was placed in the third neck and the stirred solution was cooled under an atmosphere of nitrogen to -45° C. by placing it in a methanol/water 50:50 dry ice bath. The thermometer was removed and potassium carbonate 250.21 g (1.810 mol, 100 M %) was added through a powder funnel over a 5 minute period. The reaction mixture warmed to -40° C. but there was no apparent reaction and the carbonate did not dissolve. The solution was diluted with 200 ml DMF and potassium thioacetate 407.10 g (3.564 mol, 196.9 M %) was added through a powder funnel over a 5 minute period. The powder funnel was rinsed with 300 ml DMF which was added to the reaction solution which had warmed to -30° C. The reaction was allowed to slowly warm up as the dry ice was consumed. When the reaction temperature reached -10° C. the reaction began to bubble. The reaction was allowed to warm slowly to room temperature and was stirred under nitrogen for 22 hours. Water, 2 1, and 500 ml concentrated hydrochloric acid were mixed and cooled to 9° C. in an ice bath. The tan colored reaction mixture was slowly poured into the stirred acid solution over a 25 minute period. The reaction flask was washed with 2×100 ml portions of deionized water which was added to the acid solution (10° C., pH 1.5). The acid solution was poured into a 4 l separatory funnel and was extracted sequentially with 3×500 ml and 1×250 ml ethyl acetate. Each organic extract was washed with a separate 100 ml portion of saturated sodium chloride solution. The organic extracts were combined and dried over 400 g of anhydrous sodium sulfate. The solution was filtered through a fluted filter paper into a 2,000 ml round bottom flask and the solvent was removed in two portions under reduced pressure on the rotary evaporator. The sodium sulfate was washed with 3×100 ml portions of ethyl acetate which were filtered into the 2,000 ml round bottom. After all the solvent was removed, the rotary evaporator was connected to the high-vacuum pump and the water bath was heated to 100° C. The product was removed after 1.5 hour to afford 241.07 g of the crude brown oily product which crystallized on cooling. The crystalline mass was placed under high vacuum at 22° C. for 16 hours to afford 240.51 g (82% yield) of the crude crystalline 2-acetylthio-2-methylpropanoic acid.

1. washThe flask and the funnel were rinsed with 4×100 ml portions of DMF
2. additionwere added to the reaction flask
3. customThe thermometer was removed
4. temperatureThe reaction mixture warmed to -40° C.
5. customno apparent reaction
6. additionwas added through a powder funnel over a 5 minute period
7. washThe powder funnel was rinsed with 300 ml DMF which
8. additionwas added to the reaction solution which
9. temperaturehad warmed to -30° C
10. temperatureto slowly warm up as the dry ice
11. customwas consumed
12. customreached -10° C.
13. customto bubble
14. temperatureto warm slowly to room temperature
15. additionWater, 2 1, and 500 ml concentrated hydrochloric acid were mixed
16. temperaturecooled to 9° C. in an ice bath
17. additionThe tan colored reaction mixture was slowly poured into the stirred acid solution over a 25 minute period
18. washThe reaction flask was washed with 2×100 ml portions of deionized water which
19. additionwas added to the acid solution (10° C., pH 1.5)
20. additionThe acid solution was poured into a 4 l separatory funnel
21. extractionwas extracted sequentially with 3×500 ml and 1×250 ml ethyl acetate
22. extractionEach organic extract
23. washwas washed with a separate 100 ml portion of saturated sodium chloride solution
24. dry with materialdried over 400 g of anhydrous sodium sulfate
25. filtrationThe solution was filtered through
26. filtrationa fluted filter paper into a 2,000 ml round bottom flask
27. customthe solvent was removed in two portions under reduced pressure on the rotary evaporator
28. washThe sodium sulfate was washed with 3×100 ml portions of ethyl acetate which
29. filtrationwere filtered into the 2,000 ml round bottom
30. customAfter all the solvent was removed
31. customthe rotary evaporator
32. temperaturethe water bath was heated to 100° C
33. customThe product was removed after 1.5 hour
34. customto afford 241.07 g of the crude brown oily product which
35. customcrystallized
36. temperatureon cooling
37. waitThe crystalline mass was placed under high vacuum at 22° C. for 16 hours

ORD record

ord-c4e9faad7c78432daf065cd8c7440bc4

Source dataset

uspto-grants-1991_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05026913