benzyl 2-diethoxyphosphorylacetate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). 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 the mixture was partitioned between Et2O and water the aqueous layer was washed with Et2O The organic extracts were sequentially washed with saturated KHCO3 solution and brine the combined extract was dried over MgSO4 filtered the filtrate was concentrated in vacuo The oily residue was purified by flash chromatography (silica gel, 6 cm×20 cm)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). 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 the mixture was partitioned between Et2O and water the aqueous layer was washed with Et2O The organic extracts were sequentially washed with saturated KHCO3 solution and brine the combined extract was dried over MgSO4 filtered the filtrate was concentrated in vacuo The oily residue was purified by flash chromatography (silica gel, 6 cm×20 cm)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The mixture of bromo-acetic acid benzyl ester (229 g, 1.0 mol) and phosphorous acid triethyl ester (166 g, 1.0 mol) was stirred at reflux for 10 hrs and the solvent was evaporated in vacuo to give crude (diethoxy-phosphoryl)-acetic acid benzyl ester (230 g) which was directly used for next step. at reflux for 10 hrs the solvent was evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of Example 8H (2.61 g, 9.16 mmol), benzyl diethylphosphonoacetate (2.83 g, 9.90 mmol), and sodium hydride (0.24 g, 10 mmol) in benzene (40 mL) at room temperature was stirred 2 hours, diluted with ethyl acetate, washed sequentially with saturated aqueous NH4Cl and pH 7 buffer, dried (MgSO4), filtered, and concentrated. Flash column chromatography (silica gel, 2:1 hexanes/CH2Cl2) provided the desired product. MS (ESI) m/e 419 (M+H)+. washed sequentially with saturated aqueous NH4Cl and pH 7 buffer dried (MgSO4) filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). 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 the mixture was partitioned between Et2O and water the aqueous layer was washed with Et2O The organic extracts were sequentially washed with saturated KHCO3 solution and brine the combined extract was dried over MgSO4 filtered the filtrate was concentrated in vacuo The oily residue was purified by flash chromatography (silica gel, 6 cm×20 cm)