반응 #43753

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sodium tert-butoxide

N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-3-bromo-1-benzo-thiopene-2-carboxamide hydrochloride

benzophenone-imine

rac-BINAP

→

title compound

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-amino-1-benzothiophene-2-carboxamide dihydrochloride

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후처리

1. 1
   workup.ADDITIONadded to a flask which
2. 2
   기타has been dried
3. 3
   온도by heating
4. 4
   workup.ADDITION1.5 ml of toluene are added
5. 5
   workup.ADDITION0.5 ml of THF is added
6. 6
   workup.WAITAfter a further 6 h
7. 7
   여과the mixture is filtered
8. 8
   여과(0.45 μm filter)
9. 9
   기타purified by preparative HPLC
10. 10
    workup.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. 11
    workup.WAITAfter 1 h at RT
12. 12
    농축the reaction mixture is concentrated
13. 13
    기타The solid formed
14. 14
    기타is triturated with acetonitrile
15. 15
    여과filtered off
16. 16
    기타Drying under high vacuum

실험 절차

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.

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