Cyclopropanemethanol → Cyclopropylmethyl 8-chloro-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate

HRID 1154489Notes

Reaction equation

HRID 1154489 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:25])[N:9]3[CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([O:18]C(C)(C)C)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.O[CH2:27][CH:28]1[CH2:30][CH2:29]1>CCO.CCO.CCO.CCO.[Ti]>[Cl:1][C:2]1[C:7]2[C:8](=[O:25])[N:9]3[CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([O:18][CH2:27][CH:28]3[CH2:30][CH2:29]3)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 75644CyclopropanemethanolHCID 53705407HCID 53705407, compound

Product 1

HCID 146197Cyclopropylmethyl 8-chloro-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 2724286Titanium(IV)ethoxideCatalyst

Procedure

A mixture of 9.4 g (26.1 mmol) of tert.butyl (S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate, 30 g (416 mmol) of hydroxymethyl-cyclopropane and 1.4 g (6 mmol) of tetraethyl orthotitanate is stirred at 120° for 24 hours, a small amount of solvent being distilled off in vacuo three times. The mixture is subsequently evaporated in vacuo, the residue is taken up in 60 ml of chloroform, the chloroform solution is treated with 40 ml of water and stirred for 15 hours. The mixture is then filtered through siliceous earth while washing with chloroform, the chloroform phase is dried over magnesium sulphate and evaporated. The residue is chromatographed on silica gel while eluting with ethyl acetate. After recrystallization from ethyl acetate, there is obtained cyclopropylmethyl (S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate of melting point 193-194°.

Workup

  1. distillationa small amount of solvent being distilled off in vacuo three times
  2. customThe mixture is subsequently evaporated in vacuo
  3. additionthe chloroform solution is treated with 40 ml of water
  4. stirringstirred for 15 hours
  5. filtrationThe mixture is then filtered through siliceous earth
  6. washwhile washing with chloroform
  7. dry with materialthe chloroform phase is dried over magnesium sulphate
  8. customevaporated
  9. customThe residue is chromatographed on silica gel
  10. washwhile eluting with ethyl acetate
  11. customAfter recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-49a1fc8b9d3240fc971b3967530d5f88
Source dataset
uspto-grants-1984_12
Patent number
US04489003

Reaction notes

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