Hydrochloric Acid → HCID 21993296, compound

To Grignard reagent prepared from 3-fluoro-4-trifluoromethoxy bromobenzene 70.0 g (270 mmol) and magnesium in dried THF 300 ml at room temperature, a THF (200 ml) solution of cyclohexanedione monoethyleneketal 42.1 g (270 mmol) was added dropwise at room temperature, and the mixture was stirred for 3 hours at room temperature. The reactant was added to one liter of 6N-hydrochloric acid, and the product was extracted with diethylether. The extract was washed with water, a saturated sodium bicarbonate aqueous solution, and then water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. To the residue, para-toluene sulfonic acid 5 g and toluene 500 ml were added. The mixture was refluxed with heating for 3 hours while removing water formed with Dien-Stark. The reactant was washed with water, a saturated sodium bicarbonate aqueous solution, and then water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=4/1). Such obtained purified material was hydrogenated in the presence of 5% palladium carbon 5 g as a catalyst in ethanol 300 ml. The catalyst was filtered off, the solvent was distilled off under reduced pressure, formic acid 20 g and toluene 200 ml were added to the residue, and the mixture was refluxed for 3 hours. After cooling, water 300 ml was added to the reactant, and the organic layer was fractionated, washed with water, a saturated sodium bicarbonate aqueous solution, and then water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=3/1) to obtain 4-(3-fluoro-4-trifluoromethoxyphenyl)cyclohexanone 22.0 g (84.5 mmol). The yield was 31.3% from 3-fluoro-4-trifluoromethoxybromobenzene.

1. extractionthe product was extracted with diethylether
2. washThe extract was washed with water
3. dry with materiala saturated sodium bicarbonate aqueous solution, and then water, and dried over anhydrous magnesium sulfate
4. distillationthe solvent was distilled off under reduced pressure
5. additionTo the residue, para-toluene sulfonic acid 5 g and toluene 500 ml were added
6. temperatureThe mixture was refluxed
7. temperaturewith heating for 3 hours
8. customwhile removing water
9. customformed with Dien-Stark
10. washThe reactant was washed with water
11. dry with materiala saturated sodium bicarbonate aqueous solution, and then water, and dried over anhydrous magnesium sulfate
12. distillationthe solvent was distilled off under reduced pressure
13. customThe residue was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=4/1)
14. customSuch obtained
15. custompurified material
16. filtrationThe catalyst was filtered off
17. distillationthe solvent was distilled off under reduced pressure, formic acid 20 g and toluene 200 ml
18. additionwere added to the residue
19. temperaturethe mixture was refluxed for 3 hours
20. temperatureAfter cooling
21. additionwater 300 ml was added to the reactant
22. washwashed with water
23. dry with materiala saturated sodium bicarbonate aqueous solution, and then water, and dried over anhydrous magnesium sulfate
24. distillationthe solvent was distilled off
25. customThe residue was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=3/1)

ORD record

ord-c952c3c398464e3fb91cd175f5ea9ba4

Source dataset

uspto-grants-2001_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06235355B1