反应详情

温度

-78 °C

A solution of 20 mL of a 1.0M solution of sodium hexamethyldisilamide in tetrahydrofuran was cooled to -78° C. in an ice bath under nitrogen. Then a solution of 3.0 g (20 mmole) of benzyl methyl ketone in 10 mL of dry THF was cooled to -78° C. and added dropwise by canula to the first solution. After 5 min., a pre-cooled (-78° C.) solution of 4.5 g (5 mmole) of 17-ethyl-1-hydroxy-12-[2'-(4"-oxo-3"-methoxycyclohexyl)-1'-methylvinyl]-14-t-butyldimethylsilyloxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (Example 9) in 10 mL of dry tetrahydrofuran was added dropwise over 5 minutes and the solution was stirred at -78° C. under nitrogen. After 1 h, the reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry tetrahydrofuran. Ether was added and the mixture was partitioned between ether and water and the aqueous layer was washed with ether. The two ether extracts were sequentially washed with saturated KHCO3 solution and brine, then the combined extract was dried over MgSO4, filtered and concentrated. The oily residue was purified by HPLC (silica gel, Waters RCM) using 1:3:6 acetonitrile: methyl-tert-butylether:hexanes to afford 2.36 g (46%) of the title compound as a colorless foam; NMR (CDCl3) shows distinct AB pattern at 2.6 ppm; MS (FAB) 1044 (M+Li).

1. additionadded dropwise by canula to the first solution
2. additionwas added dropwise over 5 minutes
3. waitAfter 1 h
4. customthe reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry tetrahydrofuran
5. additionEther was added
6. customthe mixture was partitioned between ether and water
7. washthe aqueous layer was washed with ether
8. washThe two ether extracts were sequentially washed with saturated KHCO3 solution and brine
9. extractionthe combined extract
10. dry with materialwas dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe oily residue was purified by HPLC (silica gel, Waters RCM)