ethyl (E)-4-oxo-4-phenylbut-2-enoate

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

Procedure: Under nitrogen atmosphere, 15 mL of THF was added to 3.05 g (5 mmol, 1.0 equivalent) of (BrZnCH2COOEt.THF)2. Under argon atmosphere, a solution of 1.02 g (5 mmol) of trans-ethyl 3-benzoylacrylate in 2.5 mL of THF was added dropwise while stirring at 0˜5° C. The mixture was stirred at 20˜25° C. for 3 hours. 7.5 mL of 1N hydrochloric acid was added dropwise at 20° C. or lower, followed by dilution with 25 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of water, 10 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.42 g of the desired product (yield 97%). The mixture was stirred at 20˜25° C. for 3 hours Then, the layers were separated The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of water, 10 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution After washing the organic layer was dried with anhydrous magnesium sulfate Concentration under reduced pressure

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

Procedure: A mixture of 7.50 g of trans-β-benzoylacrylic acid, 2.36 g of ethanol, 0.50 g of sulfuric acid and 30 ml of chloroform was refluxed for 5 hours while azeotropically removing water produced from the reaction system. After cooling, the reaction mixture was washed with a saturated solution of NaHCO and then with water. The solvent was distilled away to give 8.08 g of ethyl trans-β-benzoylacrylate. produced from the reaction system After cooling the reaction mixture was washed with a saturated solution of NaHCO The solvent was distilled away

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3.00 g of β-benzoylacrylic acid (cis/trans =1/2 according to 1H NMR analysis), 10 ml of ethanol and 0.63 g of sulfuric acid was refluxed for 2 hours. A pressure was gradually reduced with the aspirator and ethanol was distilled away for 10 minutes. After a pressure was finally reduced to 20 mmHg, the resultant was stirred at 85° C. for 40 minutes and then cooled, followed by the procedure as in Example 1 to give 2.45 g of ethyl trans-β-benzoylacrylate. was refluxed for 2 hours was distilled away for 10 minutes cooled

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 200 mg of ethyl cis-β-benzoylacrylate, 200 mg of boron trifluoride etherate (about 47 %) and 10 ml of toluene was stirred at 80° C. for 45 minutes and then cooled, followed by the procedure as in Example 1 to give 175 mg of ethyl trans-β-benzoylacrylate as a yellow oil. cooled

Conditions: temp:62.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7.75 g of trans-β-benzoylacrylic acid, 25.8 ml of ethanol and 1.63 g of sulfuric acid was stirred at 62° C. for 3 hours. A pressure was gradually reduced with the aspirator and ethanol was distilled away for 20 minutes. After a pressure was finally reduced to 20 mmHg, the resultant was stirred at 62° C. for 1.5 hours and then cooled, followed by the procedure as in Example 1 to give 8.18 g of ethyl trans-β-benzoylacrylate. was distilled away for 20 minutes the resultant was stirred at 62° C. for 1.5 hours cooled

Conditions: temp:62.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7.75 g of trans-β-benzoylacrylic acid, 25.8 ml of ethanol and 1.63 g of sulfuric acid was stirred at 62° C. for 3 hours. A pressure was gradually reduced with the aspirator and ethanol was distilled away for 20 minutes. After a pressure was finally reduced to 20 mmHg, the resultant was stirred at 62° C. for 1.5 hours and then cooled, followed by the procedure as in Example 1 to give 8.18 g of ethyl trans-β-benzoylacrylate. was distilled away for 20 minutes the resultant was stirred at 62° C. for 1.5 hours cooled

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 100 ml of ethanol were added 9.69 g of N6-trifluoroacetyl-L-lysine and 8.16 g of trans-ethyl β-benzoylacrylate. Thereto was added 40 ml of 1N aqueous solution of lithium hydroxide over about 2 hours with stirring, while maintaining the temperature at about −5° C., and the stirring was further continued for 30 minutes. The reaction was terminated by adding 10 ml of concentrated hydrochloric acid thereto. To the reaction mixture were added 130 ml of ethanol and 5 g of 10% palladium-carbon, and a reduction reaction was carried out at about 40° C. under ordinary pressure. After the reaction, the catalyst was removed by suction filtration. The obtained ethanol solution was adjusted to about pH 4 with sodium hydroxide, added with water and concentrated under reduced pressure to distil away ethanol so as to replace the solvent with water. The resulting crystals were filtered with suction and dried under vacuum to give 33 g of N2-(1-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine (1S/1R ratio =80/20). The reaction was terminated by adding 10 ml of concentrated hydrochloric acid To the reaction mixture were added 130 ml of ethanol and 5 g of 10% palladium-carbon a reduction reaction was carried out at about 40° C. under ordinary pressure After the reaction the catalyst was removed by suction filtration added with water concentrated under reduced pressure to distil away ethanol so as The resulting crystals were filtered with suction dried under vacuum

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

Procedure: Under nitrogen atmosphere, 15 mL of THF was added to 3.05 g (5 mmol, 1.0 equivalent) of (BrZnCH2COOEt.THF)2. Under argon atmosphere, a solution of 1.02 g (5 mmol) of trans-ethyl 3-benzoylacrylate in 2.5 mL of THF was added dropwise while stirring at 0˜5° C. The mixture was stirred at 20˜25° C. for 3 hours. 7.5 mL of 1N hydrochloric acid was added dropwise at 20° C. or lower, followed by dilution with 25 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of water, 10 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.42 g of the desired product (yield 97%). The mixture was stirred at 20˜25° C. for 3 hours Then, the layers were separated The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of water, 10 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution After washing the organic layer was dried with anhydrous magnesium sulfate Concentration under reduced pressure

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

Procedure: Under nitrogen atmosphere, 15 mL of THF was added to 3.05 g (5 mmol, 1.0 equivalent) of (BrZnCH2COOEt.THF)2. Under argon atmosphere, a solution of 1.02 g (5 mmol) of trans-ethyl 3-benzoylacrylate in 2.5 mL of THF was added dropwise while stirring at 0˜5° C. The mixture was stirred at 20˜25° C. for 3 hours. 7.5 mL of 1N hydrochloric acid was added dropwise at 20° C. or lower, followed by dilution with 25 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of water, 10 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.42 g of the desired product (yield 97%). The mixture was stirred at 20˜25° C. for 3 hours Then, the layers were separated The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of water, 10 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution After washing the organic layer was dried with anhydrous magnesium sulfate Concentration under reduced pressure

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

Procedure: 8.0 g (20 mmoles) of Nε -t-butoxycarbonyl-(S)-lysyl-(S)-proline-t-butylester are dissolved in 100 ml of diethyl ether and 4.48 g (22 mmoles) of E-ethyl-3-benzoyl-acrylate are added to the solution. The reaction mixture is stirred at room temperature for 5 hours. After evaporation of the solvent the title product is isolated on a Kieselgel column in the form of transparent oil. Rf =0.49 i(in a 7:3 eluent mixture of ethyl acetate and ether). After evaporation of the solvent the title product is isolated on a Kieselgel column in the form of transparent oil

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

Procedure: 4.84 g (20 mmoles) of (S)-alanyl-(S)-proline-t-butylester are dissolved in 40 ml of dry benzene and 4.08 g (20 mmoles) of E-ethyl-3-benzoyl-acrylate are added at room temperature under stirring. After one hour stirring at room temperature the solvent is evaporated off under reduced pressure, the residue is dissolved in 20 ml of ethyl acetate and 2.32 g (20 mmoles) of maleinic acid are added. The precipitated crystals are filtered off after one hour standing and washed with 20 ml of ethyl acetate. 6.7 g (60%) of product are obtained with a melting point of 109°-110° C. After one hour stirring at room temperature the solvent is evaporated off under reduced pressure the residue is dissolved in 20 ml of ethyl acetate The precipitated crystals are filtered off after one hour standing washed with 20 ml of ethyl acetate

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

Procedure: 8.0 g (20 mmoles) of Nε -t-butoxycarbonyl-(S)-lysyl-(S)-proline-t-butylester are dissolved in 100 ml of diethyl ether and 4.48 g (22 mmoles) of E-ethyl-3-benzoyl-acrylate are added to the solution. The reaction mixture is stirred at room temperature for 5 hours. After evaporation of the solvent the title product is isolated on a Kieselgel column in the form of transparent oil. Rf =0.49 i(in a 7:3 eluent mixture of ethyl acetate and ether). After evaporation of the solvent the title product is isolated on a Kieselgel column in the form of transparent oil