Glycine → 1H-1,4-Benzodiazepine-2,5-dione, 7-chloro-3,4-dihydro-1-methyl-

HRID 2223071Notes

Reaction equation

HRID 2223071 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH3:11])[C:9](=[O:12])[O:8][C:7](=O)[C:6]=2[CH:14]=1.[NH2:15][CH2:16]C(O)=O>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH3:11])[C:9](=[O:12])[CH2:16][NH:15][C:7](=[O:8])[C:6]=2[CH:14]=1

Participants

4

Reactant 2

HCID 750GlycineHCID 267242H-3,1-Benzoxazine-2,4(1H)-dione, 6-chloro-1-methyl-

Product 1

HCID 6142081H-1,4-Benzodiazepine-2,5-dione, 7-chloro-3,4-dihydro-1-methyl-

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

As illustrated in the scheme above, a mixture of 6-chloro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (6.00 g, 28.4 mmol) and glycine (2.14 g, 28.4 mmol) in glacial acetic acid (72 mL) was heated at reflux for 4 h. The reaction was cooled and concentrated in vacuo. Water was added to the residue, and the mixture was cooled to 0° C. NaHCO3 was added to adjust the pH of the aqueous layer to approximately 8, and then the aqueous layer was extracted with CH2Cl2 (3×). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was triturated with Et2O, the solvent was removed by filtration, and the resulting solid was washed with additional Et2O to provide the title compound as a slightly yellow solid (5.657 g, 89%). 1H-NMR (CDCl3): δ 7.88 (d, J=2.5 Hz, 1H), 7.57 (br s, 1H), 7.53 (dd, J=2.6 Hz, J=8.7 Hz, 1H), 7.19 (d, J=8.6 Hz, 1H), 3.84 (d, J=6.1 Hz, 2H), 3.39 (s, 3H). MS (ESI) (M+H)+=225.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated in vacuo
  5. additionWater was added to the residue
  6. additionNaHCO3 was added
  7. extractionthe aqueous layer was extracted with CH2Cl2 (3×)
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was triturated with Et2O
  12. customthe solvent was removed by filtration
  13. washthe resulting solid was washed with additional Et2O

Sources & evidence

ORD record
ord-7d3c5a6c2d0d49e39e675983f7920fc7
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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