反应详情

温度

100 °C

10-chloro-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 100; 256 mg, 1.20 mmol) was taken up in DMA (10 mL) and cooled on an ice-bath, with stirring, under nitrogen. Sodium hydride (60% in mineral oil; 232 mg, 5.8 mmol) was carefully added portionwise and the reaction mixture left to stir for 5 minutes, before removing cooling bath and stirring for a further 30 minutes. A solution of 2-chlorocyclopentanone (Aldrich; 600 uL, 6.00 mmol) in DMA (5 mL) was then added. The reaction mixture was heated to 100° C. and stirred for 3.5 hours and then allowed to cool, before addition of saturated aqueous ammonium chloride solution (1 mL). The mixture was partitioned between DCM (40 mL) and water (40 mL). Phases were separated and the aqueous phase re-extracted with DCM (40 mL). Combined extracts were washed with brine, dried over magnesium sulphate, filtered and evaporated. The residue was purified on a silica column eluting with ethyl acetate. Product containing fractions were combined and evaporated to yield the title compound as a sticky brown gum (211 mg, 60%)

1. temperaturecooled on an ice-bath
2. waitthe reaction mixture left
3. stirringto stir for 5 minutes
4. custombefore removing
5. temperaturecooling bath
6. stirringstirring for a further 30 minutes
7. stirringstirred for 3.5 hours
8. customThe mixture was partitioned between DCM (40 mL) and water (40 mL)
9. customPhases were separated
10. extractionthe aqueous phase re-extracted with DCM (40 mL)
11. washCombined extracts were washed with brine
12. dry with materialdried over magnesium sulphate
13. filtrationfiltered
14. customevaporated
15. customThe residue was purified on a silica column
16. washeluting with ethyl acetate
17. additionProduct containing fractions
18. customevaporated