Reaktion #689472

Reaktionsgleichung

4-(1-acetyl-4-piperidinylmethyl)-2-(tert -butoxycarbonyl)-aminomethylmorpholine

trifluoroacetic acid

4-amino-5-chloro-2, 3-dihydrobenzo[b]furan-7-carboxylic acid

DMF

water

→

titled compound

N-[{4-(1-acetyl-4-piperidinylmethyl)-2-morpholinyl}methyl]-4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxamide

Lösungsmittel

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction solution was dried under reduced pressure
2. 2
   workup.DISSOLUTIONthe residue was dissolved in toluene
3. 3
   Sonstigedried under reduced pressure
4. 4
   workup.ADDITIONTo the residue was added water
5. 5
   Extraktionextracted with chloroform
6. 6
   WaschenThe extract was washed with water
7. 7
   Trocknenbrine, and then dried over anhydrous magnesium sulfate
8. 8
   SonstigeThe solvent was removed in vacuo
9. 9
   workup.ADDITIONA solution of the oily residue in DMF (5 ml) containing 4-(1-acetyl-4-piperidinylmethyl)-2-aminomethylmorpholine
10. 10
    workup.ADDITIONwas added to a reaction solution which
11. 11
    Sonstigewas obtained
12. 12
    workup.STIRRINGThe mixture was stirred at room temperature overnight
13. 13
    Extraktionthe mixture was extracted with chloroform
14. 14
    Waschenthe extract was sequentially washed with saturated sodium bicarbonate, water and brine
15. 15
    Trocknendried over anhydrous magnesium sulfate
16. 16
    SonstigeThe solvent was removed in vacuo
17. 17
    SonstigeThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1)

Vorschrift

To a solution of 4-(1-acetyl-4-piperidinylmethyl)-2-(tert -butoxycarbonyl)-aminomethylmorpholine (Reference Example 15) (0.70 g) in methylene chloride (5 ml) was added trifluoroacetic acid (5 ml), and the mixture was stirred at room temperature for 2 hours. The reaction solution was dried under reduced pressure to be solidified, and the residue was dissolved in toluene, and then dried under reduced pressure to be solidified again. To the residue was added water, and the mixture was alkalified with 2N aqueous sodium hydroxide and extracted with chloroform. The extract was washed with water, then brine, and then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. A solution of the oily residue in DMF (5 ml) containing 4-(1-acetyl-4-piperidinylmethyl)-2-aminomethylmorpholine was added to a reaction solution which was obtained by stirring a solution of 4-amino-5-chloro-2, 3-dihydrobenzo[b]furan-7-carboxylic acid (0.42 g) and N,N′-carbonyldiimidazole (0.35 g) in DMF (10 ml) at room temperature for 1 hour. The mixture was stirred at room temperature overnight. To the reaction solution was added water, and the mixture was extracted with chloroform, and then the extract was sequentially washed with saturated sodium bicarbonate, water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1) to give the titled compound (0.85 g) as a white amorphous solid.

Quelle