反应详情

To diisopropylamine (4.88 mL, 34.8 mmol) in THF (33 mL) at −78° C. was added a 1.37 M solution of n-butyllithium in hexane (24.6 mL, 33.7 mmol). After stirring at the same temperature for 40 min, the LDA solution was transferred via cannula over 30 min to a solution of compound 1B (2.75 g, 11.2 mmol) in THF (112 mL) at −78° C. The reaction was stirred for 1.5 h when iodomethane (10.5 mL, 168 mmol) was added and the reaction was stirred at −78° C. for 2 h then was stored at −40° C. overnight. After warming to rt and stirring overnight, the reaction was quenched with saturated aqueous ammonium chloride. Ethyl acetate was added and the layers were separated. The organic layer was washed with brine, and the aqueous layer was back-extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure. The resulting residue was purified using preparative HPLC (Luna C-18, 30×250 mm, eluting with 40-100% solvent B (A=90% H2O-10% MeOH and B=10% H2O- 90% MeOH) over 30 min; Flow rate at 10 mL/min. UV detection at 220 nm) to provide compound 3A as a yellow oil (591 mg).

1. additionwas added
2. stirringthe reaction was stirred at −78° C. for 2 h
3. waitthen was stored at −40° C. overnight
4. stirringstirring overnight
5. customthe reaction was quenched with saturated aqueous ammonium chloride
6. additionEthyl acetate was added
7. customthe layers were separated
8. washThe organic layer was washed with brine
9. extractionthe aqueous layer was back-extracted with EtOAc
10. dry with materialThe combined organic layers were dried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe resulting residue was purified
14. washeluting with 40-100% solvent B (A=90% H2O-10% MeOH and B=10% H2O- 90% MeOH) over 30 min