2-azidoethanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of 50.0 g of 2-azidoethanol (574 mmol) in 100 mL of dry THF was added dropwise to a stirred (mechanical stirrer) suspension of 25.3 g of NaH (632 mmol), in 250 mL of dry THF over a period of 1 hour. The reaction mixture was charged with 18.5 g of tetrabutylammonium bromide (57.4 mmol) and 9.52 g of potassium iodide (57.4 mmol) in one portion. Finally, a solid addition funnel was used to add 73.6 g of sodium chloroacetate (632 mmol) to the reaction mixture. The resulting suspension was heated at reflux temperature for 20 hrs. The reaction mixture was quenched with 200 mL of water (added dropwise with cooling), and the THF was removed in vacuo. The resulting basic solution was washed with dichloromethane (8×200 mL). The aqueous extract was acidified to pH=1 (concentrated HCl), saturated with solid NaCl, and extracted with 6×350 mL of dichloromethane. The combined dichloromethane extracts were dried overnight over Na2SO4, solvent removed in vacuo to give 45.6 g of III as a yellow oil (55%). The product was used in the next coupling experiment after spectral characterization. Carbonyldiimidazole (9.83 g, 60.6 mmol) and (2-azidoethoxy)acetic acid (II) (8.00 g, 55.1 mmol) in 100 mL of dry dichloromethane were stirred at room temperature for 1 hour. A solution of 8.7 g of 2,2-dimethyl-1,3-dioxane-4,6-dione (60.6 mmol, Meldrum's acid) and 4.4 g of dry pyridine (55.1 mmol) in 30 mL of dry dichloromethane were added to the reaction mixture, and stirred for 16 hrs at room temperature. The reaction mixture was washed with aqueous 2 N HCl solution (2×60 mL), water (2×40 ml), and brine (40 mL), dried (MgSO4), and the solvent removed under reduced pressure to give 15 g of the desired product (IV) (100%). TLC showed small amounts of Meldrum's acid in the crude product. The crude product was used in the next experiment without any further purification. Finally, a solid addition funnel The resulting suspension was heated at reflux temperature for 20 hrs The reaction mixture was quenched with 200 mL of water ( added dropwise with cooling), and the THF was removed in vacuo The resulting basic solution was washed with dichloromethane (8×200 mL) The aqueous extract extracted with 6×350 mL of dichloromethane The combined dichloromethane extracts were dried overnight over Na2SO4, solvent removed in vacuo

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

Procedure: A solution of methanesulphonyl chloride (5.7 g) in methylene chloride (20 ml) was added dropwise to a stirred solution of 2-azidoethanol (4.3 g) and triethylamine (5.0 g) in methylene chloride (80 ml). After 2 hours stirring at room temperature the reaction mixture was washed with water, dried (MgSO4) and evaporated to dryness in vacuo to give the title compound as a yellow oil, yield 7 g, which was used directly without further purification. was washed with water dried (MgSO4) evaporated to dryness in vacuo

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

Procedure: 2-Azidoethanol (17.40 g, 0.2 mol), freshly distilled methylene chloride (150 mL), and Et3N (21.21 g, 0.21 mol) were added into a three-neck round-bottom flask equipped with a condenser and a dropping funnel. Under nitrogen atmosphere and magnetic stirring, freshly distilled anhydrous methylene chloride (150 mL), DMAP (1.7 g, 14 mmol), and freshly distilled anhydrous Et3N (46.5 g, 0.46 mol) were sequentially added. After the flask was immersed into an ice-water bath, 2-bromoisobutyryl bromide (48.28 g, 0.21 mol) was added dropwise into the previous solution. Twenty-four hours later, the reaction mixture was washed successively with 1 M HCl (3×200 mL) solution and deionized water (1×200 mL). The organic phase was dried over anhydrous MgSO4 overnight. After filter and removal of methylene chloride on a rotary evaporator, the obtained residues were distilled under reduced pressure to give a colorless viscous liquid. The yield was: 33.4 g, 70%. 1H NMR (CDCl3, δ, ppm): 4.24 (t, 2H, N3CH2CH2), 3.52 (t, 2H, N3CH2), 1.96 (s, 6H, (CH3)2Br). equipped with a condenser and a dropping funnel After the flask was immersed into an ice-water bath Twenty-four hours later, the reaction mixture was washed successively with 1 M HCl (3×200 mL) solution The organic phase was dried over anhydrous MgSO4 overnight After filter removal of methylene chloride on a rotary evaporator the obtained residues were distilled under reduced pressure to give a colorless viscous liquid

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Succinic anhydride (23.0 g, 0.230 mol) was added into a three-neck round-bottom flask equipped with a condenser and a dropping funnel. Under nitrogen atmosphere and magnetic stirring, freshly distilled methylene chloride (150 mL), DMAP (2.3 g, 19 mmol) and freshly distilled Et3N (46.46 g, 0.460 mol) was sequentially added. After the flask was immersed into an ice-water bath, 2-azidoethanol (20.0 g, 0.230 mol) was added dropwise into the previous solution. The solution was later heated at 40° C. for 48 h, and the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL). The organic phase was dried over anhydrous MgSO4 overnight. After filtering and removal of methylene chloride under reduced pressure, the final product was obtained as a yellow viscous liquid. The yield was: 38.4 g, 90%. 1H NMR (CDCl3, δ, ppm): 4.20 (t, 2H, N3CH2CH2), 3.42 (t, 2H, N3CH2), and 2.61 (m, 4H, CH2CH2COOH). equipped with a condenser and a dropping funnel After the flask was immersed into an ice-water bath the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL) The organic phase was dried over anhydrous MgSO4 overnight After filtering removal of methylene chloride under reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Succinic anhydride (23.0 g, 0.230 mol) was added into a three-neck round-bottom flask equipped with a condenser and a dropping funnel. Under nitrogen atmosphere and magnetic stirring, freshly distilled methylene chloride (150 mL), DMAP (2.3 g, 19 mmol) and freshly distilled Et3N (46.46 g, 0.460 mol) was sequentially added. After the flask was immersed into an ice-water bath, 2-azidoethanol (20.0 g, 0.230 mol) was added dropwise into the previous solution. The solution was later heated at 40° C. for 48 h, and the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL). The organic phase was dried over anhydrous MgSO4 overnight. After filtering and removal of methylene chloride under reduced pressure, the final product was obtained as a yellow viscous liquid. The yield was: 38.4 g, 90%. 1H NMR (CDCl3, δ, ppm): 4.20 (t, 2H, N3CH2CH2), 3.42 (t, 2H, N3CH2), and 2.61 (m, 4H, CH2CH2COOH). equipped with a condenser and a dropping funnel After the flask was immersed into an ice-water bath the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL) The organic phase was dried over anhydrous MgSO4 overnight After filtering removal of methylene chloride under reduced pressure

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

Procedure: 2-Azidoethanol (17.40 g, 0.2 mol), freshly distilled methylene chloride (150 mL), and Et3N (21.21 g, 0.21 mol) were added into a three-neck round-bottom flask equipped with a condenser and a dropping funnel. Under nitrogen atmosphere and magnetic stirring, freshly distilled anhydrous methylene chloride (150 mL), DMAP (1.7 g, 14 mmol), and freshly distilled anhydrous Et3N (46.5 g, 0.46 mol) were sequentially added. After the flask was immersed into an ice-water bath, 2-bromoisobutyryl bromide (48.28 g, 0.21 mol) was added dropwise into the previous solution. Twenty-four hours later, the reaction mixture was washed successively with 1M HCl (3×200 mL) solution and deionized water (1×200 mL). The organic phase was dried over anhydrous MgSO4 overnight. After filter and removal of methylene chloride on a rotary evaporator, the obtained residues were distilled under reduced pressure to give a colorless viscous liquid. The yield was: 33.4 g, 70%. 1H NMR (CDCl3, δ, ppm): 4.24 (t, 2H, N3CH2CH2), 3.52 (t, 2H, N3CH2), 1.96 (s, 6H, (CH3)2Br). equipped with a condenser and a dropping funnel After the flask was immersed into an ice-water bath Twenty-four hours later, the reaction mixture was washed successively with 1M HCl (3×200 mL) solution The organic phase was dried over anhydrous MgSO4 overnight After filter removal of methylene chloride on a rotary evaporator the obtained residues were distilled under reduced pressure to give a colorless viscous liquid

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Succinic anhydride (23.0 g, 0.230 mol) was added into a three-neck round-bottom flask equipped with a condenser and a dropping funnel. Under nitrogen atmosphere and magnetic stirring, freshly distilled methylene chloride (150 mL), DMAP (2.3 g, 19 mmol) and freshly distilled Et3N (46.46 g, 0.460 mol) was sequentially added. After the flask was immersed into an ice-water bath, 2-azidoethanol (20.0 g, 0.230 mol) was added dropwise into the previous solution. The solution was later heated at 40° C. for 48 h, and the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL). The organic phase was dried over anhydrous MgSO4 overnight. After filtering and removal of methylene chloride under reduced pressure, the final product was obtained as a yellow viscous liquid. The yield was: 38.4 g, 90%. 1H NMR (CDCl3, δ, ppm): 4.20 (t, 2H, N3CH2CH2), 3.42 (t, 2H, N3CH2), and 2.61 (m, 4H, CH2CH2COOH). equipped with a condenser and a dropping funnel After the flask was immersed into an ice-water bath the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL) The organic phase was dried over anhydrous MgSO4 overnight After filtering removal of methylene chloride under reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Succinic anhydride (23.0 g, 0.230 mol) was added into a three-neck round-bottom flask equipped with a condenser and a dropping funnel. Under nitrogen atmosphere and magnetic stirring, freshly distilled methylene chloride (150 mL), DMAP (2.3 g, 19 mmol) and freshly distilled Et3N (46.46 g, 0.460 mol) was sequentially added. After the flask was immersed into an ice-water bath, 2-azidoethanol (20.0 g, 0.230 mol) was added dropwise into the previous solution. The solution was later heated at 40° C. for 48 h, and the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL). The organic phase was dried over anhydrous MgSO4 overnight. After filtering and removal of methylene chloride under reduced pressure, the final product was obtained as a yellow viscous liquid. The yield was: 38.4 g, 90%. 1H NMR (CDCl3, δ, ppm): 4.20 (t, 2H, N3CH2CH2), 3.42 (t, 2H, N3CH2), and 2.61 (m, 4H, CH2CH2COOH). equipped with a condenser and a dropping funnel After the flask was immersed into an ice-water bath the reaction mixture was washed successively with 1 M HCl solution (5×100 mL) and deionized water (2×100 mL) The organic phase was dried over anhydrous MgSO4 overnight After filtering removal of methylene chloride under reduced pressure