反应详情

温度

80 °C

87 mg (0.22 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-3-bromo-1-benzo-thiopene-2-carboxamide hydrochloride, 47.1 mg (0.26 mmol) of benzophenone-imine, 12.1 mg (0.02 mmol) of rac-BINAP, 45.8 mg (0.48 mmol) of sodium tert-butoxide and 6.0 mg (0.01 mmol) of Pd2(dba)3 are, under argon, added to a flask which has been dried by heating. 1.5 ml of toluene are added, and the reaction mixture is heated at 80° C. After 30 min, 0.5 ml of THF is added, followed by a further 6.0 mg (0.01 mmol) of Pd2(dba)3 after 6 h. After a further 6 h, the mixture is filtered (0.45 μm filter) and then purified by preparative HPLC. The resulting benzophenoneimine adduct is dissolved in a 1:1 mixture of THF and methanol with addition of 20% by volume of 1N hydrochloric acid. After 1 h at RT, the reaction mixture is concentrated. The solid formed is triturated with acetonitrile and filtered off. Drying under high vacuum gives 17 mg (21% of theory) of the title compound.

1. additionadded to a flask which
2. customhas been dried
3. temperatureby heating
4. addition1.5 ml of toluene are added
5. addition0.5 ml of THF is added
6. waitAfter a further 6 h
7. filtrationthe mixture is filtered
8. filtration(0.45 μm filter)
9. custompurified by preparative HPLC
10. dissolutionThe resulting benzophenoneimine adduct is dissolved in a 1:1 mixture of THF and methanol with addition of 20% by volume of 1N hydrochloric acid
11. waitAfter 1 h at RT
12. concentrationthe reaction mixture is concentrated
13. customThe solid formed
14. customis triturated with acetonitrile
15. filtrationfiltered off
16. customDrying under high vacuum