反应详情

A solution of 7-amino-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (0.054 g, 0.175 mmol) in anhydrous N,N-dimethylformamide (0.35 mL) was cooled in an ice bath, placed under a nitrogen atmosphere, and treated with N-chlorosuccinimide (0.024 g, 0.18 mmol). The mixture was stirred at room temperature for 18.5 hours and then heated in an oil bath at 35° C. for 3 hours. The reaction mixture was partitioned between EtOAc and water, and the organic phase was dried over MgSO4, filtered, and evaporated under vacuum. The residue was purified by preparative HPLC on a YMC-Pak ODS column (2×10 cm), eluting with 0.1% TFA in 10–100% MeCN/H2O (15 min gradient) at a 20 mL/min flow rate. The product-containing fractions (UV detection at 350 nm) were diluted with EtOAc, washed with 5% NaHCO3, water, and brine, dried over MgSO4, filtered, and evaporated under vacuum. The residual film was triturated with hexanes and the solid residue was dried under a N2 stream to afford 7-amino-9a-butyl-4,8-dichloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (48 mg, 80%).

1. temperatureheated in an oil bath at 35° C. for 3 hours
2. customThe reaction mixture was partitioned between EtOAc and water
3. dry with materialthe organic phase was dried over MgSO4
4. filtrationfiltered
5. customevaporated under vacuum
6. customThe residue was purified by preparative HPLC on a YMC-Pak ODS column (2×10 cm)
7. washeluting with 0.1% TFA in 10–100% MeCN/H2O (15 min gradient) at a 20 mL/min flow rate
8. additionThe product-containing fractions (UV detection at 350 nm) were diluted with EtOAc
9. washwashed with 5% NaHCO3, water, and brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customevaporated under vacuum
13. customThe residual film was triturated with hexanes
14. customthe solid residue was dried under a N2 stream