1-azido-2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound XIX in 250 ml pyridine was added 89 g of triphenyl phospine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixutre stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 nl) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixutre stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 nl) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound XIX in 250 ml pyridine was added 89 g of triphenyl phospine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixutre stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 nl) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixutre stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 nl) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mechanically, vigorously stirred suspension of 1,11-diazido-3,6,9-trioxaundecane (20.8 g, 0.085 mol) in 5%/o hydrochloric acid (200 ml) was added a solution of triphenylphosphine (19.9 g, 0.073 mol) in ether (150 ml) over 3 hrs at room temperature. The reaction mixture was stirred for additional 24 hrs. The phases were separated and the aqueous phase was extracted with dichloromethane (3×40 ml). The aqueous phase was cooled in an ice/water bath and pH was adjusted to ca 12 by addition of KOH. The product was extracted into dichloromethane (5×50 ml). Combined organic phases were dried (MgSO4). Filtration and evaporation gave 14.0 g (88%) of yellow oil. Analysis by MALDI-TOF mass spectroscopy (matrix: α-cyano-4-hydroxycinnamic acid) gave a M+H peak at 219 as expected. Further characterisation using 1H (500 MHz) and 13C (125 MHz) NMR spectroscopy verified the structure. The phases were separated the aqueous phase was extracted with dichloromethane (3×40 ml) The aqueous phase was cooled in an ice/water bath by addition of KOH The product was extracted into dichloromethane (5×50 ml) Combined organic phases were dried (MgSO4) Filtration and evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound II in 250 ml pyridine was added 89 g of triphenyl phosphine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixture stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixture stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound XIX in 250 ml pyridine was added 89 g of triphenyl phosphine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixture stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixture stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound XIX in 250 ml pyridine was added 89 g of triphenyl phosphine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixture stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixture stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound XIX in 250 ml pyridine was added 89 g of triphenyl phospine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixutre stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 nl) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixutre stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 nl) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound XIX in 250 ml pyridine was added 89 g of triphenyl phosphine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixture stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixture stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled, stirred solution of 24.4 g of Compound XIX in 250 ml pyridine was added 89 g of triphenyl phosphine. Nitrogen bubbles evolved. The solution was stirred with ice cooling for 45 minutes and then allowed to warm to room temperature. After 45 minutes at room temperature 100 ml of concentrated ammonium hydroxide was added and the mixture stirred overnight. The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether. The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide. The aqueous phase was saturated with sodium chloride and extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml). The combined alcohol and dichloromethane extracts were concentrated under reduced pressure and the residue was taken up in 100 ml of ethanol. Concentrated hydrochloric acid (15 ml) was added and the solvent removed under reduced pressure. The residue was crystallized from ethanol/ether. The hygroscopic crystals were dried under vacuum. the mixture stirred overnight The mixture was partitioned between 500 ml of 0.5N citric acid and 250 ml of ether The aqueous phase was washed with ether (2×250 ml) to remove triphenyl phosphine oxide extracted with 1-butanol (4×250 ml) and dichloromethane (4×250 ml) The combined alcohol and dichloromethane extracts were concentrated under reduced pressure Concentrated hydrochloric acid (15 ml) was added the solvent removed under reduced pressure The residue was crystallized from ethanol/ether The hygroscopic crystals were dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mechanically, vigorously stirred suspension of 1,11-diazido-3,6,9-trioxaundecane (20.8 g, 0.085 mol) in 5% hydrochloric acid (200 ml) was added a solution of triphenylphosphine (19.9 g, 0.073 mol) in ether (150 ml) over 3 hrs at room temperature. The reaction mixture was stirred for additional 24 hrs. The phases were separated and the aqueous phase was extracted with dichloromethane (3×40 ml). The aqueous phase was cooled in an ice/water bath and pH was adjusted to ca 12 by addition of KOH. The product was extracted into dichloromethane (5×50 ml). Combined organic phases were dried (MgSO4). Filtration and evaporation gave 14.0 g (88%) of yellow oil. Analysis by MALDI-TOF mass spectroscopy (matrix: α-cyano-4-hydroxycinnamic acid) gave a M+H peak at 219 as expected. Further characterisation using 1H (500 MHz) and 13C (125 MHz) NMR spectroscopy verified the structure. The phases were separated the aqueous phase was extracted with dichloromethane (3×40 ml) The aqueous phase was cooled in an ice/water bath by addition of KOH The product was extracted into dichloromethane (5×50 ml) Combined organic phases were dried (MgSO4) Filtration and evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mechanically, vigorously stirred suspension of 1,11-diazido-3,6,9-trioxaundecane (20.8 g, 0.085 mol) in 5% hydrochloric acid (200 ml) was added a solution of triphenylphosphine (19.9 g, 0.073 mol) in ether (150 ml) over 3 hrs at room temperature. The reaction mixture was stirred for additional 24 hrs. The phases were separated and the aqueous phase was extracted with dichloromethane (3×40 ml). The aqueous phase was cooled in an ice/water bath and pH was adjusted to ca 12 by addition of KOH. The product was extracted into dichloromethane (5×50 ml). Combined organic phases were dried (MgSO4). Filtration and evaporation gave 14.0 g (88%) of yellow oil. Analysis by MALDI-TOF mass spectroscopy (matrix: α-cyano-4-hydroxycinnamic acid) gave a M+H peak at 219 as expected. Further characterisation using 1H (500 MHz) and 13C (125 MHz) NMR spectroscopy verified the structure. The phases were separated the aqueous phase was extracted with dichloromethane (3×40 ml) The aqueous phase was cooled in an ice/water bath by addition of KOH The product was extracted into dichloromethane (5×50 ml) Combined organic phases were dried (MgSO4) Filtration and evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 52 g (0.212 mol) of 1,11-diazido-3,6,9-trioxaundecane (1) were stirred with 480 ml of 5% aqueous HCl and a solution of 47.8 g (0.182 mol) PPh3 in 350 ml diethyl ether was added dropwise under stirring during a period of 45 minutes. After stirring for another 24 hours, the precipitate was filtered off and the separated aqueous layer was washed 3× with 100 mL portions of diethyl ether. Then, 41.4 g KOH were added to the aqueous layer (to pH 11) and the solution was allowed to stand at 4° C. for 16 hours. Any further precipitate was filtered off and the mixture was further basified by adding another 93 g of KOH. The product formed a second layer and was extracted 7× with 100 mL portions of DCM. The combined organic phases were dried over Na2SO4, filtered and concentrated by rotary evaporation to yield an amber oil, which was used without any further purification (35.7 g≅77% of theoretical yield). 1H-NMR (CDCl3): δ 3.68 (m, 10H), δ 3.54 (t, J=5 Hz, 2H), δ 3.39 (t, J=5 Hz, 2H), δ 2.86 (t, J=5 Hz, 2H), δ 1.49 (br, s, 2H). See Schwabacher, A. W. et al. (1998) J. Org. Chem. 63, 1727–1729. After stirring for another 24 hours the precipitate was filtered off the separated aqueous layer was washed 3× with 100 mL portions of diethyl ether Then, 41.4 g KOH were added to the aqueous layer (to pH 11) to stand at 4° C. for 16 hours Any further precipitate was filtered off by adding another 93 g of KOH The product formed a second layer was extracted 7× with 100 mL portions of DCM The combined organic phases were dried over Na2SO4 filtered concentrated by rotary evaporation to yield an amber oil, which was used without any further purification (35.7 g≅77% of theoretical yield)