反应详情

2.0 g (5.4 mmol) of tert.butyl 8-chloro-11,13a-dihydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate, 0.5 g (2.1 mmol) of tetraethyl orthotitanate and 25 ml of hydroxymethyl-cyclopropane are stirred at 130° for 23 hours, portions each of about 2 ml of solvent being distilled off in vacuo three times. The mixture is subsequently evaporated in vacuo, the residue is treated with water and chloroform, stirred for 30 minutes, filtered over siliceous earth and the organic phase is separated. The aqueous phase is extracted twice with chloroform, the organic extracts are washed once with saturated sodium chloride solution, 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 8-chloro-11,13a-dihydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate of melting point 189°-190°.

1. distillationportions each of about 2 ml of solvent being distilled off in vacuo three times
2. customThe mixture is subsequently evaporated in vacuo
3. additionthe residue is treated with water and chloroform
4. filtrationfiltered over siliceous earth
5. customthe organic phase is separated
6. extractionThe aqueous phase is extracted twice with chloroform
7. washthe organic extracts are washed once with saturated sodium chloride solution
8. dry with materialdried 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