benzyl (E)-but-2-enoate

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

Procedure: Benzyl (2E)-but-2-enoate obtained in Example 1e (20.5 g, 116 mmol) was dissolved in dichloromethane (5 ml), and the mixture was cooled in an ice bath with stirring. Trifluoroacetic acid (257 μl, 3.47 mmol) was added, and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (33.1 g, 139 mmol) was added dropwise to the reaction liquid over 15 minutes so that the internal temperature did not exceed 62° C., while washing with dichloromethane (25 ml). The reaction liquid was left to stand until it reached mom temperature and was stirred for 15 hours. The reaction liquid was concentrated and purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane) to give the title compound (38 g). the mixture was cooled in an ice bath did not exceed 62° C. while washing with dichloromethane (25 ml) The reaction liquid was left was stirred for 15 hours The reaction liquid was concentrated purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane)

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

Procedure: Crotonic acid (70 g, 812 mmol) was dissolved in N,N-dimethylformamide (467 ml), which was cooled in an ice bath under nitrogen, and potassium carbonate (61.6 g, 447 mmol) was added. Benzyl bromide (91.7 ml, 772 mmol) was added dropwise to the reaction mixture over 20 minutes. The reaction mixture was stirred at mom temperature for 18 hours. Ethyl acetate was added to the reaction mixture, which was filtered through Celite. The filtered ethyl acetate solution was washed with water, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound (142 g, yield: 99.4%). which was cooled in an ice bath under nitrogen was filtered through Celite The filtered ethyl acetate solution was washed with water The organic layer was dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: Crotonic acid (70 g, 812 mmol) was dissolved in N,N-dimethylformamide (467 ml), which was cooled in an ice bath under nitrogen, and potassium carbonate (61.6 g, 447 mmol) was added. Benzyl bromide (91.7 ml, 772 mmol) was added dropwise to the reaction mixture over 20 minutes. The reaction mixture was stirred at mom temperature for 18 hours. Ethyl acetate was added to the reaction mixture, which was filtered through Celite. The filtered ethyl acetate solution was washed with water, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound (142 g, yield: 99.4%). which was cooled in an ice bath under nitrogen was filtered through Celite The filtered ethyl acetate solution was washed with water The organic layer was dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: This compound is prepared according to the same method as that described in Example 47 Step B from 1.8 g (4.1 mmol) of 4-[N-(ethoxycarbonyl)amino]-1-[2-(3-methoxy-4-nitrophenyl)-2-oxoethyl]pyridinium bromide with benzyl crotonate in the presence of manganese oxide as oxidizing agent. 573 mg of a yellow powder are obtained. This compound is prepared

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.4 g (53.38 mmol) of benzyl crotonate, 1.8 mL (12.8 mmol) of triethylamine and 3.7 g (42.68 mmol) of manganese oxide are successively added to a solution of 5.0 g (10.67 mmol) of 4-[N-(tert-butoxycarbonyl)amino]-1-[2-(3-methoxy-4-nitrophenyl)-2-oxoethyl]pyridinium bromide in 40 mL of dimethylformamide. The reaction mixture is then heated at 90° C. for 4 hours and then filtered on a silica bed, eluting with ethyl acetate. The filtrate is poured over water and extracted with ethyl acetate. After decantation, the organic phase is washed with a saturated sodium chloride solution, dried over sodium sulfate and then concentrated under reduced pressure. The product is purified by chromatography on silica gel, eluting with a toluene/ethyl acetate (95/5 to 70/30) mixture. 2.6 g of an orange-coloured powder are obtained. filtered on a silica bed eluting with ethyl acetate The filtrate is poured over water extracted with ethyl acetate After decantation, the organic phase is washed with a saturated sodium chloride solution dried over sodium sulfate concentrated under reduced pressure The product is purified by chromatography on silica gel eluting with a toluene/ethyl acetate (95/5 to 70/30) mixture

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzyl 3-hydroxyl-butanoate (Sakaki et al., Chem. Pharm. Bull., 37, p. 2952 (1989)) (0.46 g, 2.4 mmol), CuCl (11 mg, 5 mol %), and 1 (0.7 g, 110 mol %) were combined in 20 mL of dry CH3CN and heated to 60° C. for 16 h. The reaction mixture was cooled and evaporated, followed by isolation according to the general procedure to give benzyl crotonate (0.346 g, 83%) as a mobile oil: IR 3060, 3030, 1720; 1H NMR δ 7.40-7.20 (m, 5H), 7.00 (dq, 1H, J=15.5, 6.9), 5.86 (dq, 1H, J=16.0, 1.6), 5.18 (s, 2H), 1.83 (dd, 3H, J=1.7, 6.9). The reaction mixture was cooled evaporated

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzyl crotonate (4.0 g, 22.73 mmol) in anhydrous carbon tetrachloride (20 ml) was added N-bromosuccinimide (4.045 g, 22.7 mmol). The resulting suspension was refluxed at 100° C. under nitrogen for 20 minutes. After cooling to room temperature, the solid was removed by filtration. The filtrate was evaporated under reduced pressure to dryness. The oily residue was separated on a flash column (silica, F 4×40 cm), packed with hexane. The column was eluted with 4 liters of 4% ethyl acetate. The desired product was obtained as an oil (510 mg, 9% yield). Rf: 0.4 (10% ether/hexane) 1H NMR (CDCl3): δppm 3.99 (2H, dd, J1=7.4 Hz, J2=1.3 Hz), 5.19 (2H, s), 6.07 (1H, dt, J1=15.3 Hz, J2=1.1 Hz), 7.04 (1H, m), 7.36 (5H, m). 13C NMR (CDCl3): δppm 29.0 (t), 66.5 (t), 124.2 (d), 128.2 (d), 128.3 (d), 128.5 (d), 135.8 (s), 142.2 (d), 165.2 (s). After cooling to room temperature the solid was removed by filtration The filtrate was evaporated under reduced pressure to dryness The oily residue was separated on a flash column (silica, F 4×40 cm) The column was eluted with 4 liters of 4% ethyl acetate

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

Procedure: Benzyl (2E)-but-2-enoate obtained in Example 1e (20.5 g, 116 mmol) was dissolved in dichloromethane (5 ml), and the mixture was cooled in an ice bath with stirring. Trifluoroacetic acid (257 μl, 3.47 mmol) was added, and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (33.1 g, 139 mmol) was added dropwise to the reaction liquid over 15 minutes so that the internal temperature did not exceed 62° C., while washing with dichloromethane (25 ml). The reaction liquid was left to stand until it reached mom temperature and was stirred for 15 hours. The reaction liquid was concentrated and purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane) to give the title compound (38 g). the mixture was cooled in an ice bath did not exceed 62° C. while washing with dichloromethane (25 ml) The reaction liquid was left was stirred for 15 hours The reaction liquid was concentrated purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane)

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

Procedure: Crotonic acid (70 g, 812 mmol) was dissolved in N,N-dimethylformamide (467 ml), which was cooled in an ice bath under nitrogen, and potassium carbonate (61.6 g, 447 mmol) was added. Benzyl bromide (91.7 ml, 772 mmol) was added dropwise to the reaction mixture over 20 minutes. The reaction mixture was stirred at mom temperature for 18 hours. Ethyl acetate was added to the reaction mixture, which was filtered through Celite. The filtered ethyl acetate solution was washed with water, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound (142 g, yield: 99.4%). which was cooled in an ice bath under nitrogen was filtered through Celite The filtered ethyl acetate solution was washed with water The organic layer was dried over magnesium sulfate filtered concentrated under reduced pressure