N-Methylisatoic anhydride → 10-methyl-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

HRID 917960Notes

Reaction equation

HRID 917960 reaction equation
[CH3:1][N:2]1[C:8](=[O:9])[O:7][C:5](=O)[C:4]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:3]12.[NH:14]1[CH2:21][CH2:20][CH2:19][C@H:15]1C(O)=O>C(O)C>[CH3:1][N:2]1[C:3]2[CH:13]=[CH:12][CH:11]=[CH:10][C:4]=2[C:5](=[O:7])[N:14]2[CH2:21][CH2:20][CH2:19][CH:15]2[C:8]1=[O:9]

Participants

4

Reactant 2

HCID 25160N-Methylisatoic anhydrideHCID 145742L-Proline

Product 1

HCID 985943610-methyl-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 17.7 g. of N-methyl isatoic anhydride, 11.5 g. of L-proline and 250 ml. of ethanol is heated on a steam bath for 3 hours and then concentrated to remove the ethanol. The residue is mixed with benzene and a small portion of water and the layers are separated. The benzene layer is washed twice with water and concentrated to remove the solvent. The residue is triturated with ether. The crystals which form are collected by filtration and recrystallized from ethyl acetate yielding the pure dextrorotatory isomer, melting point 120°-122°C., [α]D25 + 486°(1%, methanol).

Workup

  1. additionA mixture of 17.7 g
  2. concentrationconcentrated
  3. customto remove the ethanol
  4. additionThe residue is mixed with benzene
  5. customa small portion of water and the layers are separated
  6. washThe benzene layer is washed twice with water
  7. concentrationconcentrated
  8. customto remove the solvent
  9. customThe residue is triturated with ether
  10. filtrationThe crystals which form are collected by filtration
  11. customrecrystallized from ethyl acetate yielding the pure dextrorotatory isomer, melting point 120°-122°C., [α]D25 + 486°(1%, methanol)

Sources & evidence

ORD record
ord-ca50bdc15b90484395c996f4cf8c1af8
Source dataset
uspto-grants-1976_07
Patent number
US03968230

Reaction notes

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