(Z)-3-phenylprop-2-enamide

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of cinnamamide (25.3 g) and 1,3-dichloroacetone (20.9 g) was stirred for one hour at 130° C. The reaction mixture was diluted with water, neutralized with potassium carbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography. From the fraction eluted with diethyl ether-hexane, 4-chloromethyl-2-[(E)-2-phenylethenyl]oxazole (16.9 g, 47%) was obtained. Recrystallization from diethyl ether-hexane gave colorless needles, mp 72-73° C. extracted with ethyl acetate The ethyl acetate layer was washed with water dried (MgSO4) concentrated under reduced pressure From the fraction eluted with diethyl ether-hexane

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a suspension of 3-phenyl-acrylamide (10.31 g, 67.95 mmol) and NaHCO3 (28.47 g, 339.73 mmol) in THF (260 mL) was treated with 3-bromo-2-oxo-propionic acid ethyl ester (13.04 mL, 88.33 mmol) and the reaction mixture was heated at reflux for 15 h. 3-Bromo-2-oxo-propionic acid ethyl ester (13.04 mL, 88.33 mmol) was added again and the reaction mixture was stirred at reflux for 15 h. The reaction mixture was then filtered over celite and the solvents were evaporated under reduced pressure. The residue was dissolved in THF (30 mL) and treated at 0° C., dropwise, with trifluoroacetic anhydride (30.0 mL, 215.83 mmol). The reaction mixture was then stirred at rt overnight. Sat. aq. Na2CO3 was added and the mixture was extracted with EA (3×150 mL), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (1:9 EA-Hept) gave the title compound as a yellow solid. TLC:rf (1:9 EA-Hept)=0.1. LC-MS-conditions 02: tR=1.01 min; [M+H]+=244.48. the reaction mixture was heated at reflux for 15 h at reflux for 15 h The reaction mixture was then filtered over celite the solvents were evaporated under reduced pressure The residue was dissolved in THF (30 mL) treated at 0° C. The reaction mixture was then stirred at rt overnight the mixture was extracted with EA (3×150 mL) dried over MgSO4 filtered the solvent was removed under reduced pressure Purification of the residue by FC (1:9 EA-Hept)

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

Procedure: Cinnamamide (1.9 g, 13 mmol) was mixed with chlorocarbonylsulphenylchloride (1.0 mL, 13 mmol) in chloroform and heated to reflux for 18 h. The reaction mixture was concentrated in vacuo and the resultant material was taken up in boiling hexane (100 mL). The solvent was decanted from the remaining solid, the volume of this solution was reduced by half, and the solution was allowed to cool. The crystalline solids which formed were collected and washed with hexane to afford 5-[(E)-2-phenylethenyl]-1,3,4-oxathiazol-2-one (1.93 g, 72% yield) as pale yellow needles. M.p. 105–106° C. 1H NMR (DMSO-d6, 300 MHz) δ 7.52 (m, 3H), 7.46 (s, 0.5H), 7.41 (m, 2.5H), 6.63 (d, J=16 Hz, 1H). heated to reflux for 18 h The reaction mixture was concentrated in vacuo The solvent was decanted from the remaining solid to cool The crystalline solids which formed were collected washed with hexane

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cinnamamide (2.0 g, 14 mmol), chloroacetone (0.93 mL, 16 mmol), and K2CO3 (940 mg, 6.8 mmol) were combined under argon and the mixture was heated in a 120° C. oil bath. The reaction mixture solidified and stirring stopped upon heating. After 16 h, the cooled reaction mixture was quenched by the addition of water (20 mL) and then diluted with ethyl acetate (100 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography eluting with 90:10 hexane:ethyl acetate. The product that was obtained (280 mg) showed some close running impurities by thin layer chromatography (TLC). The material was further purified by preparative TLC via multiple elutions with 95:5 hexane:ethyl acetate. Isolation of the middle of the main band afforded 4-methyl-2-[(E)-2-phenylethenyl]-1,3-oxazole (47.0 mg, 2% yield) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.53-7.32 (m, 7H), 6.91 (d, J=16.4 Hz, 1H), 2.21 (s, 3H). MS (ESI) 185.7 (M++H). upon heating the cooled reaction mixture was quenched by the addition of water (20 mL) diluted with ethyl acetate (100 mL) The organic phase was dried over Na2SO4 filtered concentrated in vacuo The crude product was purified by column chromatography eluting with 90:10 hexane The product that was obtained (280 mg) The material was further purified by preparative TLC via multiple elutions with 95:5 hexane

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cinnamamide (2.0 g, 14 mmol), chloroacetone (0.93 mL, 16 mmol), and K2CO3 (940 mg, 6.8 mmol) were combined under argon and the mixture was heated in a 120° C. oil bath. The reaction mixture solidified and stirring stopped upon heating. After 16 h, the cooled reaction mixture was quenched by the addition of water (20 mL) and then diluted with ethyl acetate (100 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography eluting with 90:10 hexane:ethyl acetate. The product that was obtained (280 mg) showed some close running impurities by thin layer chromatography (TLC). The material was further purified by preparative TLC via multiple elutions with 95:5 hexane:ethyl acetate. Isolation of the middle of the main band afforded 4-methyl-2-[(E)-2-phenylethenyl]-1,3-oxazole (47.0 mg, 2% yield) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.53-7.32 (m, 7H), 6.91 (d, J=16.4 Hz, 1H), 2.21 (s, 3H). MS (ESI) 185.7 (M++H). upon heating the cooled reaction mixture was quenched by the addition of water (20 mL) diluted with ethyl acetate (100 mL) The organic phase was dried over Na2SO4 filtered concentrated in vacuo The crude product was purified by column chromatography eluting with 90:10 hexane The product that was obtained (280 mg) The material was further purified by preparative TLC via multiple elutions with 95:5 hexane

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

Procedure: Synthesis was conducted in accordance with the report (J. Org. Chem., 1996, Vol. 61, p. 6496) by Panek et al. Sodium hydrogencarbonate (22.8 g) and ethyl bromopyruvate (10.5 ml) were added to a solution of cinnamamide (10.0 g) in tetrahydrofuran (250 ml) at room temperature, and the mixture was heated under reflux for 48 hours. The reaction mixture was allowed to cool to room temperature, filtered through Celite and then concentrated under reduced pressure to obtain residue. Trifluoroacetic anhydride (30 ml) was added to a solution of this residue in tetrahydrofuran (30 ml) at 0° C., and the mixture was gradually warmed to room temperature. After the mixture was stirred for 63 hours, a saturated aqueous solution (500 ml) of sodium hydrogencarbonate and ethyl acetate (150 ml) were added to the reaction mixture, and a water layer was separated. The water layer was extracted with ethyl acetate (150 ml). The organic layers were combined, washed with saturated aqueous solution of sodium chloride (150 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1) to obtain the title compound (10.9 g). Synthesis the mixture was heated under reflux for 48 hours filtered through Celite concentrated under reduced pressure to obtain residue the mixture was gradually warmed to room temperature a water layer was separated The water layer was extracted with ethyl acetate (150 ml) washed with saturated aqueous solution of sodium chloride (150 ml) dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1)

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

Procedure: Synthesis was conducted in accordance with the report (J. Org. Chem., 1996, Vol. 61, p. 6496) by Panek et al. Sodium hydrogencarbonate (22.8 g) and ethyl bromopyruvate (10.5 ml) were added to a solution of cinnamamide (10.0 g) in tetrahydrofuran (250 ml) at room temperature, and the mixture was heated under reflux for 48 hours. The reaction mixture was allowed to cool to room temperature, filtered through Celite and then concentrated under reduced pressure to obtain residue. Trifluoroacetic anhydride (30 ml) was added to a solution of this residue in tetrahydrofuran (30 ml) at 0° C., and the mixture was gradually warmed to room temperature. After the mixture was stirred for 63 hours, a saturated aqueous solution (500 ml) of sodium hydrogencarbonate and ethyl acetate (150 ml) were added to the reaction mixture, and an organic layer was separated. The water layer was extracted with ethyl acetate (150 ml). The organic layers were combined, washed with saturated saline (150 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1) to obtain the title compound (10.9 g) as a colorless solid. Synthesis the mixture was heated under reflux for 48 hours filtered through Celite concentrated under reduced pressure to obtain residue the mixture was gradually warmed to room temperature an organic layer was separated The water layer was extracted with ethyl acetate (150 ml) washed with saturated saline (150 ml) dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1)

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

Procedure: Synthesis was conducted in accordance with the report (J. Org. Chem., 1996, Vol. 61, p. 6496) by Panek et al. Sodium hydrogencarbonate (22.8 g) and ethyl bromopyruvate (10.5 ml) were added to a solution of cinnamamide (10.0 g) in tetrahydrofuran (250 ml) at room temperature, and the mixture was heated under reflux for 48 hours. The reaction mixture was allowed to cool to room temperature, filtered through Celite and then concentrated under reduced pressure to obtain residue. Trifluoroacetic anhydride (30 ml) was added to a solution of this residue in tetrahydrofuran (30 ml) at 0° C., and the mixture was gradually warmed to room temperature. After the mixture was stirred for 63 hours, a saturated aqueous solution (500 ml) of sodium hydrogencarbonate and ethyl acetate (150 ml) were added to the reaction mixture, and an organic layer was separated. The water layer was extracted with ethyl acetate (150 ml). The organic layers were combined, washed with saturated saline (150 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1) to obtain the title compound (10.9 g) as a colorless solid. Synthesis the mixture was heated under reflux for 48 hours filtered through Celite concentrated under reduced pressure to obtain residue the mixture was gradually warmed to room temperature an organic layer was separated The water layer was extracted with ethyl acetate (150 ml) washed with saturated saline (150 ml) dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1)

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

Procedure: Synthesis was conducted in accordance with the report (J. Org. Chem., 1996, Vol. 61, p. 6496) by Panek et al. Sodium hydrogencarbonate (22.8 g) and ethyl bromopyruvate (10.5 ml) were added to a solution of cinnamamide (10.0 g) in tetrahydrofuran (250 ml) at room temperature, and the mixture was heated under reflux for 48 hours. The reaction mixture was allowed to cool to room temperature, filtered through Celite and then concentrated under reduced pressure to obtain residue. Trifluoroacetic anhydride (30 ml) was added to a solution of this residue in tetrahydrofuran (30 ml) at 0° C., and the mixture was gradually warmed to room temperature. After the mixture was stirred for 63 hours, a saturated aqueous solution (500 ml) of sodium hydrogencarbonate and ethyl acetate (150 ml) were added to the reaction mixture, and an organic layer was separated. The water layer was extracted with ethyl acetate (150 ml). The organic layers were combined, washed with saturated saline (150 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1) to obtain the title compound (10.9 g) as a colorless solid. Synthesis the mixture was heated under reflux for 48 hours filtered through Celite concentrated under reduced pressure to obtain residue the mixture was gradually warmed to room temperature an organic layer was separated The water layer was extracted with ethyl acetate (150 ml) washed with saturated saline (150 ml) dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1→3:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of cinnamamide (25.3 g) and 1,3-dichloroacetone (20.9 g) was stirred for one hour at 130° C. The reaction mixture was diluted with water, neutralized with potassium carbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography. From the fraction eluted with diethyl ether-hexane, 4-chloromethyl-2-[(E)-2-phenylethenyl]oxazole (16.9 g, 47%) was obtained. Recrystallization from diethyl ether-hexane gave colorless needles, mp 72-73° C. extracted with ethyl acetate The ethyl acetate layer was washed with water dried (MgSO4) concentrated under reduced pressure From the fraction eluted with diethyl ether-hexane

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of cinnamamide (25.3 g) and 1,3-dichloroacetone (20.9 g) was stirred for one hour at 130° C. The reaction mixture was diluted with water, neutralized with potassium carbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography. From the fraction eluted with diethyl ether-hexane, 4-chloromethyl-2-[(E)-2-phenylethenyl]oxazole (16.9 g, 47%) was obtained. Recrystallization from diethyl ether-hexane gave colorless needles, mp 72-73° C. extracted with ethyl acetate The ethyl acetate layer was washed with water dried (MgSO4) concentrated under reduced pressure From the fraction eluted with diethyl ether-hexane

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

Procedure: Cinnamamide (3.27 g) was dissolved in tetrahydrofuran (33 ml), and Lawesson's reagent (4.94 g) was added. The mixture was refluxed for 3 h and methyl 4-bromo-3-oxopentanoate (6.97 g) was added. The mixture was further refluxed for 11 h. Tetrahydrofuran was evaporated under reduced pressure and ethyl acetate (300 ml) was added to the obtained residue. The mixture was washed with water (200 ml) and then with saturated brine (200 ml), and dried (Na2SO4). Ethyl acetate was evaporated under reduced pressure and the obtained residue was purified by column chromatography to give methyl (5-methyl-2-styrylthiazole-4-yl)acetate (2.9 g). The mixture was refluxed for 3 h The mixture was further refluxed for 11 h Tetrahydrofuran was evaporated under reduced pressure and ethyl acetate (300 ml) was added to the obtained residue The mixture was washed with water (200 ml) with saturated brine (200 ml), and dried (Na2SO4) Ethyl acetate was evaporated under reduced pressure the obtained residue was purified by column chromatography