(E)-1-bromobut-2-ene

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

Procedure: 3.86 g (168 mmol) of sodium metal were dissolved in 106 ml of anhydrousethanol. 36.35 g (168 mmol) of diethyl acetamidomalonate dissolved in 225 ml of anhydrous ethanol were added and the mixture was heated under refluxfor 10 minutes. 22.66 g (168 mmol) of (E)-1-bromo-2-butene were added dropwise at room temperature and the mixture was stirred overnight and then evaporated to dryness under a vacuum. The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid. The organic phase was washed with saturated sodium hydrogen carbonate solution and then with saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The solvent was evaporated to give 40 g of diethyl (E)-2-acetamido-2-(2-butenyl)malonate as a colourless oil; 1H NMR (250 MHz, CDCl3) δ: 1.25 (t, 6 H), 1.6 (d, 3 H), 2.0 (s, 3 H), 2.9 (d, 2 H), 4.2 (q, 4 H), 5.15 (m, 1 H) 5.5 (m, 1 H), 6.7 s, 1 H). were added the mixture was heated under refluxfor 10 minutes evaporated to dryness under a vacuum The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid The organic phase was washed with saturated sodium hydrogen carbonate solution with saturated sodium chloride solution and dried over anhydrous magnesium sulphate The solvent was evaporated

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

Procedure: 3.86 g (168 mmol) of sodium metal were dissolved in 106 ml of anhydrous ethanol. 36.35 g (168 mmol) of diethyl acetamidomalonate dissolved in 225 ml of anhydrous ethanol were added and the mixture was heated under reflux for 10 minutes. 22.66 g (168 mmol) of (E)-1-bromo-2-butene were added dropwise at room temperature and the mixture was stirred overnight and then evaporated to dryness under a vacuum. The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid. The organic phase was washed with saturated sodium hydrogen carbonate solution and then with saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The solvent was evaporated to give 40 g of diethyl (E)-2-acetamido-2-(2-butenyl)malonate as a colourless oil; 1H NMR (250 MHz, CDCl3) d: 1.25 (t, 6H), 1.6 (d, 3H), 2.0 (s, 3H), 2.9 (d, 2H), 4.2 (q, 4H), 5.15 (m, 1H) 5.5 (m, 1H), 6.7 s, 1H). were added the mixture was heated under reflux for 10 minutes evaporated to dryness under a vacuum The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid The organic phase was washed with saturated sodium hydrogen carbonate solution with saturated sodium chloride solution and dried over anhydrous magnesium sulphate The solvent was evaporated

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 143.1 g (836 mmol) of N-trifluoroacetylglycine in 1 L of DMF is chilled to −8° C. as 100 mL (844 mmol) of E-crotyl bromide is added dropwise, followed by addition of 140 mL (937 mmol) of DBU at −5° C. After 1.5 h at −5° C. and 2 h at −2° C. the mixture is allowed to warm to 25° C. The mixture is cooled to 0° C. and 40 mL more DBU is added. After warming to 25° C. the mixture is concentrated in vacuo. 1 L of 1:1 ether-water is added. The organic layer is separated, washed with water, 1 N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. Drying and concentration in vacuo is followed by trituration of the oil with hexanes-EtOAC to provide a solid. Chromatography on silica gel (elution with 3:1 hexanes-EtOAc) affords 49.96 g of (2E)-2-buten-1-yl N-trifluoroacetylglycinate as an oil. is added dropwise 2 h at −2° C. The mixture is cooled to 0° C. After warming to 25° C. the mixture is concentrated in vacuo 1 L of 1:1 ether-water is added The organic layer is separated washed with water, 1 N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride Drying concentration in vacuo to provide a solid

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 143.1 g (836 mmol) of N-trifluoroacetylglycine in 1 L of DMF is chilled to −8° C. as 100 mL (844 mmol) of E-crotyl bromide is added dropwise, followed by addition of 140 mL (937 mmol) of DBU at −5° C. After 1.5 h at −5° C. and 2 h at −2° C. the mixture is allowed to warm to 25° C. The mixture is cooled to 0° C. and 40 mL more DBU is added. After warming to 25° C. the mixture is concentrated in vacuo. 1 L of 1:1 ether-water is added. The organic layer is separated, washed with water, 1 N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. Drying and concentration in vacuo is followed by trituration of the oil with hexanes-EtOAC to provide a solid. Chromatography on silica gel (elution with 3:1 hexanes-EtOAc) affords 49.96 g of (2E)-2-buten-1-yl N-trifluoroacetylglycinate as an oil. is added dropwise 2 h at −2° C. The mixture is cooled to 0° C. After warming to 25° C. the mixture is concentrated in vacuo 1 L of 1:1 ether-water is added The organic layer is separated washed with water, 1 N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride Drying concentration in vacuo to provide a solid

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

Procedure: 3.86 g (168 mmol) of sodium metal were dissolved in 106 ml of anhydrousethanol. 36.35 g (168 mmol) of diethyl acetamidomalonate dissolved in 225 ml of anhydrous ethanol were added and the mixture was heated under refluxfor 10 minutes. 22.66 g (168 mmol) of (E)-1-bromo-2-butene were added dropwise at room temperature and the mixture was stirred overnight and then evaporated to dryness under a vacuum. The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid. The organic phase was washed with saturated sodium hydrogen carbonate solution and then with saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The solvent was evaporated to give 40 g of diethyl (E)-2-acetamido-2-(2-butenyl)malonate as a colourless oil; 1H NMR (250 MHz, CDCl3) δ: 1.25 (t, 6 H), 1.6 (d, 3 H), 2.0 (s, 3 H), 2.9 (d, 2 H), 4.2 (q, 4 H), 5.15 (m, 1 H) 5.5 (m, 1 H), 6.7 s, 1 H). were added the mixture was heated under refluxfor 10 minutes evaporated to dryness under a vacuum The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid The organic phase was washed with saturated sodium hydrogen carbonate solution with saturated sodium chloride solution and dried over anhydrous magnesium sulphate The solvent was evaporated

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

Procedure: 3.86 g (168 mmol) of sodium metal were dissolved in 106 ml of anhydrousethanol. 36.35 g (168 mmol) of diethyl acetamidomalonate dissolved in 225 ml of anhydrous ethanol were added and the mixture was heated under refluxfor 10 minutes. 22.66 g (168 mmol) of (E)-1-bromo-2-butene were added dropwise at room temperature and the mixture was stirred overnight and then evaporated to dryness under a vacuum. The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid. The organic phase was washed with saturated sodium hydrogen carbonate solution and then with saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The solvent was evaporated to give 40 g of diethyl (E)-2-acetamido-2-(2-butenyl)malonate as a colourless oil; 1H NMR (250 MHz, CDCl3) δ: 1.25 (t, 6 H), 1.6 (d, 3 H), 2.0 (s, 3 H), 2.9 (d, 2 H), 4.2 (q, 4 H), 5.15 (m, 1 H) 5.5 (m, 1 H), 6.7 s, 1 H). were added the mixture was heated under refluxfor 10 minutes evaporated to dryness under a vacuum The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid The organic phase was washed with saturated sodium hydrogen carbonate solution with saturated sodium chloride solution and dried over anhydrous magnesium sulphate The solvent was evaporated

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

Procedure: This compound was prepared from 2-mercaptophenol and (E)-2-butenyl bromide in 97% yield according to the general procedure for 16p in Example VII. Colorless oil; 1H NMR (CDCl3): δ 1.61 (d, J=0.8 Hz, 3H), 3.26 (d, J=7.40 Hz, 2H), 5.26-5.33 (m, 1H), 5.43-5.50 (m, 1H), 6.73 (s, 1H), 6.87 (dt, J=1.35 Hz, J=7.40 Hz, 1H), 6.99 (dd, J=1.10 Hz, 8.25 Hz, 1H), 7.27 (dt, J=1.65 Hz, J=7.40 Hz, 1H), 7.43 (dd, J=1.65 Hz, J=7.70 Hz, 1H); 13C NMR (CDCl3): δ 17.79, 39.40, 114.69, 118.57, 120.59, 125.77, 128.88, 131.27, 136.65, 157.28.

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

Procedure: 3.86 g (168 mmol) of sodium metal were dissolved in 106 ml of anhydrous ethanol. 36.35 g (168 mmol) of diethyl acetamidomalonate dissolved in 225 ml of anhydrous ethanol were added and the mixture was heated under reflux for 10 minutes. 22.66 g (168 mmol) of (E)-1-bromo-2-butene were added dropwise at room temperature and the mixture was stirred overnight and then evaporated to dryness under a vacuum. The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid. The organic phase was washed with saturated sodium hydrogen carbonate solution and then with saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The solvent was evaporated to give 40 g of diethyl (E)-2-acetamido-2-(2-butenyl)malonate as a colourless oil; 1H NMR (250 MHz, CDCl3) d: 1.25 (t, 6H), 1.6 (d, 3H), 2.0 (s, 3H), 2.9 (d, 2H), 4.2 (q, 4H), 5.15 (m, 1H) 5.5 (m, 1H), 6.7 s, 1H). were added the mixture was heated under reflux for 10 minutes evaporated to dryness under a vacuum The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid The organic phase was washed with saturated sodium hydrogen carbonate solution with saturated sodium chloride solution and dried over anhydrous magnesium sulphate The solvent was evaporated

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 143.1 g (836 mmol) of N-trifluoroacetylglycine in 1 L of DMF is chilled to −8° C. as 100 mL (844 mmol) of E-crotyl bromide is added dropwise, followed by addition of 140 mL (937 mmol) of DBU at −5° C. After 1.5 h at −5° C. and 2 h at −2° C. the mixture is allowed to warm to 25° C. The mixture is cooled to 0° C. and 40 mL more DBU is added. After warming to 25° C. the mixture is concentrated in vacuo. 1 L of 1:1 ether-water is added. The organic layer is separated, washed with water, 1 N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. Drying and concentration in vacuo is followed by trituration of the oil with hexanes-EtOAC to provide a solid. Chromatography on silica gel (elution with 3:1 hexanes-EtOAc) affords 49.96 g of (2E)-2-buten-1-yl N-trifluoroacetylglycinate as an oil. is added dropwise 2 h at −2° C. The mixture is cooled to 0° C. After warming to 25° C. the mixture is concentrated in vacuo 1 L of 1:1 ether-water is added The organic layer is separated washed with water, 1 N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride Drying concentration in vacuo to provide a solid

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

Procedure: 3.86 g (168 mmol) of sodium metal were dissolved in 106 ml of anhydrousethanol. 36.35 g (168 mmol) of diethyl acetamidomalonate dissolved in 225 ml of anhydrous ethanol were added and the mixture was heated under refluxfor 10 minutes. 22.66 g (168 mmol) of (E)-1-bromo-2-butene were added dropwise at room temperature and the mixture was stirred overnight and then evaporated to dryness under a vacuum. The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid. The organic phase was washed with saturated sodium hydrogen carbonate solution and then with saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The solvent was evaporated to give 40 g of diethyl (E)-2-acetamido-2-(2-butenyl)malonate as a colourless oil; 1H NMR (250 MHz, CDCl3) δ: 1.25 (t, 6 H), 1.6 (d, 3 H), 2.0 (s, 3 H), 2.9 (d, 2 H), 4.2 (q, 4 H), 5.15 (m, 1 H) 5.5 (m, 1 H), 6.7 s, 1 H). were added the mixture was heated under refluxfor 10 minutes evaporated to dryness under a vacuum The residue was partitioned between ethyl acetate and 0.1M hydrochloric acid The organic phase was washed with saturated sodium hydrogen carbonate solution with saturated sodium chloride solution and dried over anhydrous magnesium sulphate The solvent was evaporated