Cesium carbonate → HCID 178500653、化合物

温度

180 °C

Benzophenone imine (5.8 mL, 34.7 mmol) was added to a mixed solution of trans [4-(4-trifluoromethanesulfonyloxyphenyl)cyclohexyl]acetic acid methyl ester (12 g, 31.54 mmol), cesium carbonate (11.3 g, 34.7 mmol), palladium acetate (708 mg, 3.15 mmol), X-phos (3 g, 6.31 mmol) and toluene (78 mL) in a sealed tube. The mixture was purified 5 times with nitrogen and stirred at 180° C. for 10 hours. The prepared solution was cooled to remove the solvent under reduced pressure, the residue was sectioned with ether (600 mL) and water (600 mL) to separate each layer. The aqueous solution layer was extracted with ether (3×180 mL), a mixed organic layer was dried with anhydrous Na2SO4 and concentrated under vacuum to obtain yellow oil. The obtained oil was used without further purification (crude 21 g). The oil was dissolved in methanol (252 mL) and the solution was cooled to be 4° C. Hydrochloric acid (84 mL) 1M was slowly added thereto while maintaining the temperature less than 7° C. The solution was warmed up for 16 hours to ensure the temperature was ambient temperature. Then, methanol was removed in a vacuum state and the reaction mixture was diluted with water (210 mL). The liquid-phase mixture was washed with ether (2×180 mL) and the mixed organic layer was washed with 1M hydrochloric acid (2×90 mL). The mixed aqueous solution layer was basified with a 10% sodium carbonate solution up to pH of 9 to thereby obtain a filtrate. Ethyl acetate (3200 mL) was added thereto to thereby separate each layer. The organic layer was dried with MgSO4 and concentrated in a vacuum state until a filtrate was formed. The mixture was cooled, filtered, and washed with heptane (24 mL) to obtain trans[4-(4-aminophenyl)cyclohexyl]acetic acid methyl ester (4.247% was obtained by two steps) as a white solid.

1. customThe mixture was purified 5 times with nitrogen
2. temperatureThe prepared solution was cooled
3. customto remove the solvent under reduced pressure
4. customto separate each layer
5. extractionThe aqueous solution layer was extracted with ether (3×180 mL)
6. dry with materiala mixed organic layer was dried with anhydrous Na2SO4
7. concentrationconcentrated under vacuum
8. customto obtain yellow oil
9. customThe obtained oil was used without further purification (crude 21 g)
10. dissolutionThe oil was dissolved in methanol (252 mL)
11. temperaturethe solution was cooled
12. customto be 4° C
13. additionHydrochloric acid (84 mL) 1M was slowly added
14. temperaturewhile maintaining the temperature less than 7° C
15. temperatureThe solution was warmed up for 16 hours
16. customwas ambient temperature
17. customThen, methanol was removed in a vacuum state
18. additionthe reaction mixture was diluted with water (210 mL)
19. washThe liquid-phase mixture was washed with ether (2×180 mL)
20. washthe mixed organic layer was washed with 1M hydrochloric acid (2×90 mL)
21. customto thereby obtain a filtrate
22. customto thereby separate each layer
23. dry with materialThe organic layer was dried with MgSO4
24. concentrationconcentrated in a vacuum state until a filtrate
25. customwas formed
26. temperatureThe mixture was cooled
27. filtrationfiltered
28. washwashed with heptane (24 mL)

ORDレコード

ord-029a9c4d9c9740f085d8fdc681e411a5

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09321728B2