1,2-bis(2-iodoethoxy)ethane

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,2-bis(2-iodoethoxy)ethane (1.0 eq) was mixed with triethyl phosphate (1 eq) then heated to 160° C. for 20 minutes by microwave. The crude mixture was purified by flash chromatography on a COMBIFLASH™ system using 85-100% EtOAc/Hex to give diethyl 2-(2-(2-iodoethoxy)ethoxy)ethylphosphonate as a colorless oil. The crude mixture was purified by flash chromatography on a COMBIFLASH™ system

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,2-bis(2-iodoethoxy)ethane (1.0 eq) was mixed with triethyl phosphate (1 eq) then heated to 160° C. for 20 minutes by microwave. The crude mixture was purified by flash chromatography on a COMBIFLASH™ system using 85-100% EtOAc/Hex to give diethyl 2-(2-(2-iodoethoxy)ethoxy)ethylphosphonate as a colorless oil. The crude mixture was purified by flash chromatography on a COMBIFLASH™ system

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

Procedure: 10 ml of 1,2-bis(2-iodoethoxy)-ethane was dropped into the solution of 20 mmole 5-mercapto-1H-1,2,3-triazole (sodium salt) in 20 ml ethanol, and stirred for 24 hours at room temperature. After the solvent was evaporated in vacuum, the residual was separated with silica gel column. Elution with hexane/ethylacetate (1/3) first, and then with pure ethyl acetate gave 2.70 g product as viscous solid. Yield: 88%. 1H NMR (CDCl3): δ(ppm) 7.72 (2H, s), 3.74 (4H, t, JH-H=6.19), 3.65 (4H, s), 3.07 (4H, t, JH-H=6.19). After the solvent was evaporated in vacuum the residual was separated with silica gel column Elution with hexane/ethylacetate (1/3) first

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,2-bis(2-iodoethoxy)ethane (1.0 eq) was mixed with triethyl phosphate (1 eq) then heated to 160° C. for 20 minutes by microwave. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 85-100% EtOAc/Hex to give diethyl 2-(2-(2-iodoethoxy)ethoxy)ethylphosphonate as a colorless oil. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

Procedure: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the solution. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,2-bis(2-iodoethoxy)ethane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phases were extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phases were extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

Procedure: The title compound was prepared by using a similar procedure as described for the preparation of 21 except that 1,2-bis-(2-iodoethyloxy)ethane was used instead of 2-(diethylamino)ethyl chloride hydrochloride. This produced the crude product which was purified by flash silica gel column chromatography, eluting with 4:1 hexanes/ethyl acetate to give 43 (3.85 g, 52%) as a clear oil: MS (ES+) m/z 407.0 (M+H)+. This produced the crude product which

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

Procedure: The title compound was prepared by using a similar procedure as described for the preparation of 21 except that 1,2-bis-(2-iodoethyloxy)ethane was used instead of 2-(diethylamino)ethyl chloride hydrochloride. This produced the crude product which was purified by flash silica gel column chromatography, eluting with 4:1 hexanes/ethyl acetate to give 43 (3.85 g, 52%) as a clear oil: MS (ES+) m/z 407.0 (M+H)+. This produced the crude product which

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

Procedure: By following the process described in Example R65, Example R67 is prepared by dimerization of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol with 1-iodo-2-[2-(2-iodoethoxy)ethoxy]ethane (Example R5). A white powder is obtained. A white powder is obtained

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

Procedure: By following the process described in Example R65, Example R67 is prepared by dimerization of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol with 1-iodo-2-[2-(2-iodoethoxy)ethoxy]ethane (Example R5). A white powder is obtained. A white powder is obtained

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,2-bis(2-iodoethoxy)ethane (1.0 eq) was mixed with triethyl phosphate (1 eq) then heated to 160° C. for 20 minutes by microwave. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 85-100% EtOAc/Hex to give diethyl 2-(2-(2-iodoethoxy)ethoxy)ethylphosphonate as a colorless oil. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

Procedure: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the solution. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,2-bis(2-iodoethoxy)ethane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phases were extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phases were extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)

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

Procedure: To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n-butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. The mixture was then cooled down to −78° C., and diethyl difluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the solution. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution was added a cooled solution of 1,2-bis(2-iodoethoxy)ethane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4Cl solution. The aqueous phases were extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil. dropwise at 0° C The mixture was then cooled down to −78° C. Then the mixture was stirred at −78° C. for 40 minutes and to the resulting solution After 1.5 hours the reaction was quenched by pouring into saturated NH4Cl solution The aqueous phases were extracted with ethyl acetate three times The combined organic phases were washed with brine dried over anhydrous sodium sulfate concentrated en vaccuo The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO)