反応 #44864

反応方程式

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

収率 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

収率 73.0%

溶媒

CH2Cl2

CH2Cl2

反応条件

後処理

1. 1
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 2 hrs
2. 2
   洗浄This mixture was washed with 0.5 N HCl aq (100 mL)
3. 3
   洗浄the organic layer was washed with saturated NaHCO3 aq (75 ml)
4. 4
   濃縮the organic layer was concentrated
5. 5
   workup.ADDITIONThe residue was diluted with EtOAc (75 mL) and it
6. 6
   濃縮was concentrated until ca 15 mL
7. 7
   workup.STIRRINGthis mixture was stirred at room temperature for 30 min
8. 8
   その他During this procedure, the solid was formed
9. 9
   ろ過this mixture was filtered
10. 10
    その他Obtained solid
11. 11
    洗浄was washed with EtOAc (10 mL)
12. 12
    その他dried at 50° C. under vacuum

実験手順

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.

出典