L-Azetidine-2-carboxylic acid → (S)-5,6-difluoro-1,2,4,9,10,10a-hexahydro-azeto[2,1-c][1,4]benzodiazepine-4,10-dione

HRID 1378009Notes

Reaction equation

HRID 1378009 reaction equation
[F:1][C:2]1[C:7]2[C:8](=[O:13])O[C:10](=[O:12])[NH:11][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14].[CH2:15]1[C@@H:18](C(O)=O)[NH:17][CH2:16]1>CN(C)C=O.C(O)(=O)C>[F:1][C:2]1[C:7]2[C:8](=[O:13])[N:17]3[CH2:18][CH2:15][C@H:16]3[C:10](=[O:12])[NH:11][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14]

Participants

5

Reactant 2

HCID 16486L-Azetidine-2-carboxylic acidHCID 229144245,6-difluoro-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione

Product 1

HCID 53731819(S)-5,6-difluoro-1,2,4,9,10,10a-hexahydro-azeto[2,1-c][1,4]benzodiazepine-4,10-dioneYield 68.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 19.6 g (98.4 mmol) of 5,6-difluoro-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione and 9.95 g (98.4 mmol) of L-azetidine-2-carboxylic acid in 125 ml of dimethylformamide and 25 ml of acetic acid was stirred at 120° for 16 hours. The brown solution was evaporated and the brown residue obtained was crystallized from ethanol. There were obtained 16 g (68%) of (S)-5,6-difluoro-1,2,4,9,10,10a-hexahydro-azeto[2,1-c][1,4]benzodiazepine-4,10-dione as colourless needles of m.p. >250°.

Workup

  1. customThe brown solution was evaporated
  2. customthe brown residue obtained
  3. customwas crystallized from ethanol

Sources & evidence

ORD record
ord-624011c1d91642a9b940fcda4725df73
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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