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., 20 mL of a 1M solution of triisopropoxytitanium chloride in dichloromethane was added and the solution grew deep orange. After 10 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-butyl-dimethylsilyloxy-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. The cloudy mixture was filtered through Celite 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:hexane to afford 3.15 g (61%) of the title compound as a colorless foam; NMR (CDCl3) shows singlet at 2.1 ppm; MS (FAB) 1044 (M+Li).

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