Benzyl (diethoxyphosphoryl)acetate → 17-Ethyl-1-hydroxy-12-[2'-(4"-[benzyloxycarbonylmethylidenyl]-3"-methoxycyclohexyl)-1'-methylvinyl]-14-tert-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

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Reaction Conditions

Reaction Steps

A solution of 20 mL of a 1.0 M solution of sodium hexamethyldisilamide in THF was cooled to 0° C. in an ice bath under nitrogen. Then a solution of 5.85 g (20 mmole) of benzyl diethylphosphonoacetate in 10 mL of dry THF was added and the solution was stirred at 0° C. under nitrogen. After 15 min., the solution was cooled to -40° C. (dry ice-acetonitrile bath) under nitrogen, and 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 -40° C. under nitrogen. After 3 hr, the reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry THF. Et2O was added and the mixture was partitioned between Et2O and water and the aqueous layer was washed with Et2O. The organic extracts were sequentially washed with saturated KHCO3 solution and brine, then the combined extract was dried over MgSO4, filtered and the filtrate was concentrated in vacuo. The oily residue was purified by flash chromatography (silica gel, 6 cm×20 cm) using ethyl acetate-hexane to afford 3.28 g (63%) of the title compound as a colorless foam; NMR (CDCl3) indicated about a 9:1 mixture of E::Z olefin isomers; MS (FAB) 1042 (M+Li).

Provenance & Evidence