Reaction #1879

Reaction equation

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

acetic anhydride

triethylamine

→

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

Solvents

methanol

Conditions

Workup

1. 1
   TemperatureThe mixture was heated for one hour
2. 2
   Temperatureunder reflux
3. 3
   ConcentrationThe reaction mixture was concentrated under reduced pressure, which
4. 4
   Extractionwas subjected to extraction with ethyl acetate
5. 5
   WashThe organic layer was washed with an aqueous solution of potassium hydrogensulfate
6. 6
   Dryingan aqueous solution of sodium hydrogencarbonate and water, which was then dried
7. 7
   workup.DISTILLATIONby distilling off the solvent
8. 8
   workup.DISSOLUTIONThe residue was dissolved in 4 ml of methanol, to which
9. 9
   workup.ADDITIONwas added 2 ml of a 5% aqueous solution of potassium carbonate
10. 10
    workup.STIRRINGThe mixture was stirred for 30 minutes at 60° C
11. 11
    ConcentrationThe reaction mixture was concentrated under reduced pressure, to which
12. 12
    workup.ADDITIONwas added 1N hydrochloric acid
13. 13
    Extractionfollowed by extraction with ethyl acetate
14. 14
    WashThe organic layer was washed with water
15. 15
    Otherdried
16. 16
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure

Procedure

In 4 ml of methanol was dissolved 60 mg 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. To the solution were added 0.2 ml of acetic anhydride and 0.2 ml of triethylamine. The mixture was heated for one hour under reflux while stirring. The reaction mixture was concentrated under reduced pressure, which was subjected to extraction with ethyl acetate. The organic layer was washed with an aqueous solution of potassium hydrogensulfate, an aqueous solution of sodium hydrogencarbonate and water, which was then dried, followed by distilling off the solvent. The residue was dissolved in 4 ml of methanol, to which was added 2 ml of a 5% aqueous solution of potassium carbonate. The mixture was stirred for 30 minutes at 60° C. The reaction mixture was concentrated under reduced pressure, to which was added 1N hydrochloric acid to acidify the solution, followed by extraction with ethyl acetate. The organic layer was washed with water and dried, then the solvent was distilled off under reduced pressure. From the residue, 45 mg of N-[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ylmethyl]-N-acetyl glycine was obtained as crystals, m.p. 143°-145° C.

Source