Cesium carbonate → HCID 178500653, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence