Reaktion #44864

Reaktionsgleichung

1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one

chloroformic acid 4-nitrophenyl ester

4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylic acid 4-methylbenzenesulfonate

Et3N

→

titled compound

Ausbeute 73.0%

4-{[4-({[(3-Isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylic acid

Ausbeute 73.0%

Lösungsmittel

CH2Cl2

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 2 hrs
2. 2
   WaschenThis mixture was washed with 0.5 N HCl aq (100 mL)
3. 3
   Waschenthe organic layer was washed with saturated NaHCO3 aq (75 ml)
4. 4
   Einengenthe organic layer was concentrated
5. 5
   workup.ADDITIONThe residue was diluted with EtOAc (75 mL) and it
6. 6
   Einengenwas concentrated until ca 15 mL
7. 7
   workup.STIRRINGthis mixture was stirred at room temperature for 30 min
8. 8
   SonstigeDuring this procedure, the solid was formed
9. 9
   Filtrationthis mixture was filtered
10. 10
    SonstigeObtained solid
11. 11
    Waschenwas washed with EtOAc (10 mL)
12. 12
    Sonstigedried at 50° C. under vacuum

Vorschrift

A mixture of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (1.0 g, 5.7 mmol) and chloroformic acid 4-nitrophenyl ester (1.14 g, 5.7 mmol) in CH2Cl2 (20 mL) was stirred at room temperature for 5 under N2. To this mixture, Et3N (1.7 mL, 12.5 mmol) was added slowly and this generated mixture was added to a mixture of 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylic acid 4-methylbenzenesulfonate (2.4 g, 5.7 mmol, Step 12) in CH2Cl2 (15 mL) at rt. The resulting mixture was stirred at room temperature for 2 hrs. This mixture was washed with 0.5 N HCl aq (100 mL) and the organic layer was washed with saturated NaHCO3 aq (75 ml) then the organic layer was concentrated. The residue was diluted with EtOAc (75 mL) and it was concentrated until ca 15 mL. After seeding of the product, this mixture was stirred at room temperature for 30 min. During this procedure, the solid was formed and this mixture was filtered. Obtained solid was washed with EtOAc (10 mL), dried at 50° C. under vacuum to give 1.9 g (73%) of the titled compound as white solid.

Quelle