Reaktion #1878

Reaktionsgleichung

N-[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ylmethyl]glycine

formalin

oxalic acid

→

N-[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ylmethyl]-N-methylglycine

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was concentrated under reduced pressure
2. 2
   Extraktionthe concentrate was subjected to 5 extraction with ethyl acetate
3. 3
   WaschenThe organic layer was washed with an aqueous solution of sodium hydrogencarbonate
4. 4
   Sonstigeby drying
5. 5
   workup.DISTILLATIONThe solvent was distilled off under reduced pressure
6. 6
   workup.DISSOLUTIONThe residue was dissolved in 6 ml of methanol
7. 7
   workup.ADDITIONTo the solution were added 0.2 g of potassium carbonate and 2 ml of water
8. 8
   EinengenThe reaction mixture was concentrated under reduced pressure, to which
9. 9
   workup.ADDITIONwas added water
10. 10
    Extraktionfollowed-by extraction with ether
11. 11
    Extraktionfollowed by extraction with methylene chloride
12. 12
    WaschenThe organic layer was washed with water
13. 13
    Sonstigedried
14. 14
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure

Vorschrift

To 0.13 g of ethyl ester of N-[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ylmethyl]glycine obtained in Example 40 were added 2 ml of formalin and 2 ml of oxalic acid: The mixture was heated at 80° C. for 2 hours. The reaction mixture was concentrated under reduced pressure, and the concentrate was subjected to 5 extraction with ethyl acetate. The organic layer was washed with an aqueous solution of sodium hydrogencarbonate, then with water, followed by drying. The solvent was distilled off under reduced pressure. The residue was dissolved in 6 ml of methanol. To the solution were added 0.2 g of potassium carbonate and 2 ml of water. The mixture was stirred for 2 hours at 60° C. The reaction mixture was concentrated under reduced pressure, to which was added water, followed-by extraction with ether. The aqueous layer was acidified to pH 4 with dilute hydrochloric acid, followed by extraction with methylene chloride. The organic layer was washed with water and dried, then the solvent was distilled off under reduced pressure. From the residue was obtained 0.1 g of N-[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ylmethyl]-N-methylglycine as crystals, m.p. 195°-197° C.

Quelle