反应详情

A solution of tert-butyl 3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (example 12, step a) (8.2 g) in THF (100 mL) was treated dropwise with borane THF complex (1M in THF, 91 mL) and the resultant mixture heated at 55° C. for 2 hours. Borane dimethylsulfide complex (2M in THF, 15.17 mL) was added and the resultant mixture heated at 55° C. for 2 hours. The mixture was cooled to room temperature and quenched with methanol, then the solvents were evaporated under reduced pressure. The residue was dissolved in methanol (250 mL) and the solution treated with N1,N2-dimethylethane-1,2-diamine (10 g) and the resultant mixture was heated at reflux for 6 hours. Further N1,N2-dimethylethane-1,2-diamine (3 g) was added and heated at reflux continued for 6 hours. The mixture was cooled to room temperature and the solvents evaporated under reduced pressure, the residue was purified by flash silica chromatography eluting with 1% triethylamine and 5% methanol in dichloromethane. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 7.40 g.

1. customquenched with methanol
2. customthe solvents were evaporated under reduced pressure
3. dissolutionThe residue was dissolved in methanol (250 mL)
4. additionthe solution treated with N1,N2-dimethylethane-1,2-diamine (10 g)
5. temperaturethe resultant mixture was heated
6. temperatureat reflux for 6 hours
7. additionFurther N1,N2-dimethylethane-1,2-diamine (3 g) was added
8. temperatureheated
9. temperatureat reflux
10. temperatureThe mixture was cooled to room temperature
11. customthe solvents evaporated under reduced pressure
12. customthe residue was purified by flash silica chromatography
13. washeluting with 1% triethylamine and 5% methanol in dichloromethane
14. customPure fractions were evaporated to dryness