methyl 3-phenylprop-2-ynoate

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

Procedure: A solution of phenylacetylene (2 mmol), chlorohydroquinone(HQ-Cl) (0.4 mmol), molybdovanadophosphate (NPMoV) (35 mg) and palladium (II) acetate (50 mg) in methanol (10 mL) is stirred under CO/O2 (10 atm/0.5 atm) at 25° C. for 15 h. The reaction is then quenched with wet ether and the product is extracted with n-hexane. After removal of the solvent under reduced pressure, the product is isolated by column chromatography over silica gel (hexane ethyl acetate 5:1) to give pure methyl phenylpropiolate. The reaction is then quenched with wet ether the product is extracted with n-hexane After removal of the solvent under reduced pressure the product is isolated by column chromatography over silica gel (hexane ethyl acetate 5:1)

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

Procedure: A solution of phenylacetylene (2 mmol), chlorohydroquinone(HQ-Cl) (0.4 mmol), molybdovanadophosphate (NPMoV) (35 mg) and palladium (II) acetate (50 mg) in methanol (10 mL) is stirred under CO/O2 (10 atm/0.5 atm) at 25° C. for 15 h. The reaction is then quenched with wet ether and the product is extracted with n-hexane. After removal of the solvent under reduced pressure, the product is isolated by column chromatography over silica gel (hexane ethyl acetate 5:1) to give pure methyl phenylpropiolate. The reaction is then quenched with wet ether the product is extracted with n-hexane After removal of the solvent under reduced pressure the product is isolated by column chromatography over silica gel (hexane ethyl acetate 5:1)

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

Procedure: A solution of TDMPP (1.4 g) and palladium acetate (700 mg) in THF (200 ml) is stirred for 15 min at room temperature and methyl phenylpropiolate (10 g, 62.5 mmol) is then added. The reaction medium is stirred for 5 min at room temperature and trimethyl-silylacetylene (87.5 mmol) is then added. Stirring is continued overnight at room temperature. The reaction medium is concentrated and filtered through silica. Stirring is continued overnight at room temperature The reaction medium is concentrated filtered through silica

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

Procedure: To a solution of 2-[(aminooxy)sulfonyl]-1,3,5-trimethylbenzene (about 16.4 mmol) in acetonitrile (80 mL) was added a solution of 6,7-dihydro-5H-cyclopenta[c]pyridin-7-ylacetonitrile (1.30 g, 8.22 mmol) in acetonitrile (40 mL), and the mixture was stirred at room temperature for 30 min. N,N-Dimethylformamide (40 mL) was added, and the mixture was concentrated under reduced pressure. To 46% of the residual solution were added methyl 3-phenylpropiolate (671 μL, 4.55 mmol) and potassium carbonate (1.31 g, 9.48 mmol), and the mixture was stirred at room temperature for 18 hr. The reaction solution was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=25/75) to give the title compound (523 mg). the mixture was concentrated under reduced pressure the mixture was stirred at room temperature for 18 hr the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate/hexane=25/75)

Conditions: temp:28.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl phenylpropiolate (methyl dehydrocinnamate (0.96 g, 6 mmol)) is dissolved in acetic anhydride (14 ml) and brought to the boiling temperature of acetic anhydride in a hot oil bath (140° C.). The total amount of 1-(4-fluorobenzoyl)pyrrolidine-2-carboxylic acid (1.42 g, 6 mmol) is added, and the thoroughly mixed solution is refluxed (1 28° C.) for 20 h with stirring. After standing for 4 hours and cooling to RT, a pure crystalline solid deposits (TLC: Al2O3, diisopropyl ether, Rf 0.7). The crystals are filtered off with suction, washed with water (20 ml) and finally with isopropyl ether (10 ml). The dried crystals weigh 650 mg (32.5% of theory) (140° C.) cooling to RT The crystals are filtered off with suction washed with water (20 ml) and finally with isopropyl ether (10 ml)

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

Procedure: To a solution of 2-chloro-6-fluorobenzoylchloride oxime (1.04 g, 5.00 mmol) and methyl-3-phenyl-2-propynoate (1.20 g, 7.50 mmol) in Et2O (25 ml) at 0° C. under nitrogen was added a solution of triethyl amine (0.834 ml, 6.00 mmol) in Et2O (3 ml) over 1 h. The reaction was allowed to warm to room temperature overnight (17 h). The mixture was diluted with Et2O and H2O, the layers separated, and the organic fraction was dried (MgSO4). Column chromatography (silica gel, hexane/Et2O gradient) gave the title compound (1.53 g, 92%). the layers separated the organic fraction was dried (MgSO4)

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

Procedure: To a solution of 2-chloro-6-fluorobenzoylchloride oxime (1.04 g, 5.00 mmol) and methyl-3-phenyl-2-propynoate (1.20 g, 7.50 mmol) in Et2O (25 ml) at 0° C. under nitrogen was added a solution of triethyl amine (0.834 ml, 6.00 mmol) in Et2O (3 ml) over 1 h. The reaction was allowed to warm to room temperature overnight (17 h). The mixture was diluted with Et2O and H2O, the layers separated, and the organic fraction was dried (MgSO4). Column chromatography (silica gel, hexane/Et2O gradient) gave the title compound (1.53 g, 92%). the layers separated the organic fraction was dried (MgSO4)

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

Procedure: Dichloromethane (10 mL) and 3-Iodopyridine (928 mg, 4.53 mmol) were charged to a 100 mL, round-bottomed flask equipped with a magnetic stir bar. This colorless solution was cooled on an ice bath and O-(mesitylsulfonyl)hydroxylamine (975 mg, 4.53 mmol) in dichloromethane (10 mL) was added dropwise over 5 minutes. After to stirring at room temperature for 30 minutes, the solvent was removed by rotary evaporation to give a white solid. Methyl phenylpropiolate (1000 mg, 6.24 mmol) was added in dimethylformamide (9 mL). Potassium carbonate (2504 mg, 18.12 mmol) was added. Reaction slowly turned dark green. After stirring at room temp for 2 hours, the reaction was poured into diethyl ether (300 mL and extracted 8×25 mL water. The solvent was removed from the organic portion by rotary evaporation. The crude product was dissolved in a minimum amount of dichloromethane and charged to a 90 g “Single Sep” silica gel cartridge and eluted with 0 to 40% ethyl acetate in hexanes over 1000 mL. The title compound (200 mg, 12%) was isolated as an orange solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 3.83 (s, 3H) 7.46 (m, 3H) 7.59 (dd, J=9.16, 1.53 Hz, 1H) 7.7.5 (m, 2H) 8.00 (dd, J=9.31, 0.76 Hz, 1H) 8.82 (s, 1H). LCMS: 2.4 minutes, M+1=379. equipped with a magnetic stir bar This colorless solution was cooled on an ice bath the solvent was removed by rotary evaporation to give a white solid Reaction slowly turned dark green After stirring at room temp for 2 hours extracted 8×25 mL water The solvent was removed from the organic portion by rotary evaporation The crude product was dissolved in a minimum amount of dichloromethane charged to a 90 g “Single Sep” silica gel cartridge eluted with 0 to 40% ethyl acetate in hexanes over 1000 mL

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

Procedure: A solution of phenylacetylene (10, 2 mmol), chlorohydroquinone(HQ-Cl) (0.4 mmol), molybdovanadophosphate (NPMoV) (35 mg) and palladium (II) acetate (50 mg) in methanol (10 mL) is stirred under CO/O2 (10 atm/0.5 atm) at 25° C. for 15 h. The reaction is then quenched with wet ether and the product is extracted with n-hexane. After removal of the solvent under reduced pressure, the product is isolated by column chromatography over silica gel (hexane:ethyl acetate 5:1) to give pure methyl phenylpropiolate. The reaction is then quenched with wet ether the product is extracted with n-hexane After removal of the solvent under reduced pressure the product is isolated by column chromatography over silica gel (hexane:ethyl acetate 5:1)

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

Procedure: Dichloromethane (10 mL) and 3-Iodopyridine (928 mg, 4.53 mmol) were charged to a 100 mL round-bottomed flask equipped with a magnetic stir bar. This colorless solution was cooled on an ice bath and O-(mesitylsulfonyl)hydroxylamine (975 mg, 4.53 mmol) in dichloromethane (10 mL) was added dropwise over 5 minutes. After to stirring at room temperature for 30 minutes, the solvent was removed by rotory evaporation to give a white solid. Methyl phenylpropiolate (1000 mg, 6.24 mmol) was added in dimethylformamide (9 mL). Potassium carbonate (2504 mg, 18.12 mmol) was added. Reaction slowly turned dark green. After stirring at room temp for 2 hours, the reaction was poured into diethyl ether (300 mL and extracted 8×25 mL water. The solvent was removed from the organic portion by rotory evaporation. The crude product was dissolved in a minimum amount of dichloromethane and charged to a 90 g “Single Sep” silica gel cartridge and eluted with 0 to 40% ethyl acetate in hexanes over 1000 mL. The title compound (200 mg, 12%) was isolated as an orange solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 3.83 (s, 3H) 7.46 (m, 3H) 7.59 (dd, J=9.16, 1.53 Hz, 1H) 7.75 (m, 2H) 8.00 (dd, J=9.31, 0.76 Hz, 1H) 8.82 (s, 1H). LCMS: 2.4 minutes, M+1=379. equipped with a magnetic stir bar This colorless solution was cooled on an ice bath the solvent was removed by rotory evaporation to give a white solid Reaction slowly turned dark green After stirring at room temp for 2 hours extracted 8×25 mL water The solvent was removed from the organic portion by rotory evaporation The crude product was dissolved in a minimum amount of dichloromethane charged to a 90 g “Single Sep” silica gel cartridge eluted with 0 to 40% ethyl acetate in hexanes over 1000 mL

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

Procedure: Dichloromethane (10 mL) and 3-Iodopyridine (928 mg, 4.53 mmol) were charged to a 100 mL, round-bottomed flask equipped with a magnetic stir bar. This colorless solution was cooled on an ice bath and O-(mesitylsulfonyl)hydroxylamine (975 mg, 4.53 mmol) in dichloromethane (10 mL) was added dropwise over 5 minutes. After to stirring at room temperature for 30 minutes, the solvent was removed by rotary evaporation to give a white solid. Methyl phenylpropiolate (1000 mg, 6.24 mmol) was added in dimethylformamide (9 mL). Potassium carbonate (2504 mg, 18.12 mmol) was added. Reaction slowly turned dark green. After stirring at room temp for 2 hours, the reaction was poured into diethyl ether (300 mL and extracted 8×25 mL water. The solvent was removed from the organic portion by rotary evaporation. The crude product was dissolved in a minimum amount of dichloromethane and charged to a 90 g “Single Sep” silica gel cartridge and eluted with 0 to 40% ethyl acetate in hexanes over 1000 mL. The title compound (200 mg, 12%) was isolated as an orange solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 3.83 (s, 3H) 7.46 (m, 3H) 7.59 (dd, J=9.16, 1.53 Hz, 1H) 7.7.5 (m, 2H) 8.00 (dd, J=9.31, 0.76 Hz, 1H) 8.82 (s, 1H). LCMS: 2.4 minutes, M+1=379. equipped with a magnetic stir bar This colorless solution was cooled on an ice bath the solvent was removed by rotary evaporation to give a white solid Reaction slowly turned dark green After stirring at room temp for 2 hours extracted 8×25 mL water The solvent was removed from the organic portion by rotary evaporation The crude product was dissolved in a minimum amount of dichloromethane charged to a 90 g “Single Sep” silica gel cartridge eluted with 0 to 40% ethyl acetate in hexanes over 1000 mL

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

Procedure: A solution of phenylacetylene (10, 2 mmol), chlorohydroquinone(HQ-Cl) (0.4 mmol), molybdovanadophosphate (NPMoV) (35 mg) and palladium (II) acetate (50 mg) in methanol (10 mL) is stirred under CO/O2 (10 atm/0.5 atm) at 25° C. for 15 h. The reaction is then quenched with wet ether and the product is extracted with n-hexane. After removal of the solvent under reduced pressure, the product is isolated by column chromatography over silica gel (hexane:ethyl acetate 5:1) to give pure methyl phenylpropiolate. The reaction is then quenched with wet ether the product is extracted with n-hexane After removal of the solvent under reduced pressure the product is isolated by column chromatography over silica gel (hexane:ethyl acetate 5:1)