反应详情

A flame dried Schlenk flask, evacuated and purged with nitrogen, was charged with alkyne 88 (1.50 g, 5.46 mmol, 1 eq.). Anhydrous CH2Cl2 (35 ml) was added and the reaction stirred at r.t. Zr(Cp)2HCl (2.82 g, 10.9 mmol, 2 eq.) was added as a solid, in portions. The yellow suspension was stirred at r.t. for 1 h. The resulting yellow solution was cooled to 0° C. and iodine (1.52 g, 6.01 mmol, 1.1 eq.) added as a solid, in one portion. The cooling bath was removed and the reaction mixture stirred at room temperature for 1 h. The reaction mixture was poured into water (100 ml) and extracted with 40/60 petroleum ether (4×50 ml). The combined organic phases were washed with water (100 ml), saturated Na2S2O3 solution (2×100 ml) and brine (100 ml) before being dried (MgSO4), filtered, and concentrated to give the crude material. This was purified by flash chromatography, eluting with 40/60 petroleum ether. The fractions containing product were combined and washed with saturated Na2S2O3 solution (20 ml), dried (MgSO4), filtered, and concentrated to give the title compound 89 (1.98 g, 90%) as a clear, colourless oil. Analytical data consistent with the literature (Sato, F. et al., EP 1211241 A1, Taisho Pharmaceutical co., LTD (2002)).

1. customA flame dried Schlenk flask
2. customevacuated
3. custompurged with nitrogen
4. stirringThe yellow suspension was stirred at r.t. for 1 h
5. temperatureThe resulting yellow solution was cooled to 0° C.
6. customThe cooling bath was removed
7. stirringthe reaction mixture stirred at room temperature for 1 h
8. additionThe reaction mixture was poured into water (100 ml)
9. extractionextracted with 40/60 petroleum ether (4×50 ml)
10. washThe combined organic phases were washed with water (100 ml), saturated Na2S2O3 solution (2×100 ml) and brine (100 ml)
11. dry with materialbefore being dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customto give the crude material
15. customThis was purified by flash chromatography
16. washeluting with 40/60 petroleum ether
17. additionThe fractions containing product
18. washwashed with saturated Na2S2O3 solution (20 ml)
19. dry with materialdried (MgSO4)
20. filtrationfiltered
21. concentrationconcentrated