Reaktion #43753

Reaktionsgleichung

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

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONadded to a flask which
2. 2
   Sonstigehas been dried
3. 3
   Temperaturby 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
   Filtrationthe mixture is filtered
8. 8
   Filtration(0.45 μm filter)
9. 9
   Sonstigepurified 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
    Einengenthe reaction mixture is concentrated
13. 13
    SonstigeThe solid formed
14. 14
    Sonstigeis triturated with acetonitrile
15. 15
    Filtrationfiltered off
16. 16
    SonstigeDrying under high vacuum

Vorschrift

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.

Quelle