Cyclopropanemethanol → HCID 22828758, compound

HRID 1154487Notes

Reaction equation

HRID 1154487 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15]([O:17]C(C)(C)C)=[O:16])=[C:10]3[C@@H:9]3[CH2:22][CH2:23][N:8]3[C:7](=[O:24])[C:6]=2[CH:25]=1.O[CH2:27][CH:28]1[CH2:30][CH2:29]1>CCO.CCO.CCO.CCO.[Ti]>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15]([O:17][CH2:27][CH:28]4[CH2:30][CH2:29]4)=[O:16])=[C:10]3[C@@H:9]3[CH2:22][CH2:23][N:8]3[C:7](=[O:24])[C:6]=2[CH:25]=1

Participants

4

Reactant 2

HCID 75644CyclopropanemethanolHCID 57160017HCID 57160017, compound

Product 1

HCID 22828758HCID 22828758, compound

Reagents, catalysts & solvents 1

HCID 2724286Titanium(IV)ethoxideCatalyst

Procedure

A mixture of 2.95 g (8.6 mmol) of tert.butyl (S)-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate, 10 g of hydroxymethyl-cyclopropane and 1.6 g (6.8 mmol) of tetraethyl orthotitanate is stirred at 120° for 24 hours, about 3 ml of solvent being distilled off in vacuo after 1 hour. The mixture is subsequently evaporated in vacuo, the residue is dissolved in 40 ml of chloroform, the chloroform solution is treated with 30 ml of water and stirred for 1.25 hours. The mixture is filtered through siliceous earth, washed with chloroform, the chloroform phase is dried over magnesium sulphate and evaporated. The crude product is chromatographed on silica gel while eluting with ethyl acetate. After recrystallization from ethyl acetate/n-hexane, there is obtained cyclopropylmethyl (S)-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate of melting point 171°-172°.

Workup

  1. distillationabout 3 ml of solvent being distilled off in vacuo after 1 hour
  2. customThe mixture is subsequently evaporated in vacuo
  3. dissolutionthe residue is dissolved in 40 ml of chloroform
  4. additionthe chloroform solution is treated with 30 ml of water
  5. stirringstirred for 1.25 hours
  6. filtrationThe mixture is filtered through siliceous earth
  7. washwashed with chloroform
  8. dry with materialthe chloroform phase is dried over magnesium sulphate
  9. customevaporated
  10. customThe crude product is chromatographed on silica gel
  11. washwhile eluting with ethyl acetate
  12. customAfter recrystallization from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-5c387ab6d4ba4ac3b6533f31106c0c6b
Source dataset
uspto-grants-1984_12
Patent number
US04489003

Reaction notes

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