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

HRID 1782

Reaction equation

HRID 1782 reaction equation
[CH2:1]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:13]=2[C@@H:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:26])[O:11][C@H:10]([CH2:27][NH:28][CH2:29][C:30]([OH:32])=[O:31])[C:9]1=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:36](O)(=O)C(O)=O>>[CH2:1]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:13]=2[C@@H:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:26])[O:11][C@H:10]([CH2:27][N:28]([CH3:36])[CH2:29][C:30]([OH:32])=[O:31])[C:9]1=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 712FormaldehydeHCID 971Oxalic AcidHCID 69947765N-[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ylmethyl]glycine

Product 1

HCID 69947507N-[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ylmethyl]-N-methylglycine

Conditions

Temperature
80 °C

Procedure

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.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionthe concentrate was subjected to 5 extraction with ethyl acetate
  3. washThe organic layer was washed with an aqueous solution of sodium hydrogencarbonate
  4. customby drying
  5. distillationThe solvent was distilled off under reduced pressure
  6. dissolutionThe residue was dissolved in 6 ml of methanol
  7. additionTo the solution were added 0.2 g of potassium carbonate and 2 ml of water
  8. concentrationThe reaction mixture was concentrated under reduced pressure, to which
  9. additionwas added water
  10. extractionfollowed-by extraction with ether
  11. extractionfollowed by extraction with methylene chloride
  12. washThe organic layer was washed with water
  13. customdried
  14. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-e1cdebf350904ceba1f779d1bab6a752
Source dataset
uspto-grants-1998_03
Patent number
US05726306

Linked notes

Loading…