2-(3-fluorophenyl)acetyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 68 ml thioanisole in 600 ml dichloromethane at 0° C., were added slowly in a series aluminum chloride (77.3 g) and (3-fluorophenyl)acetyl chloride (100 g). The reaction mixture was stirred for an hour, after which 1 L of aqueous HCl was added slowly to the reaction mixture. The quenched mixture was stirred for another hour, which was followed by extraction with methylene chloride. The organic layer was washed with brine and then was dried over anhydrous magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resulting residue was purified by recrystallization from hexane/dichloromethane to yield 142.9 g of 2-(3-fluorophenyl)-1-{4-(methylthio)-phenyl}-ethanone. mp: 94.5-95.5° C. NMR: δ2.52 (s, 3H), 4.23 (s, 2H), 6.95-7.05 (m, 3H),7.25-7.30 (m, 3H), 7.92 (d, J=8.7 Hz, 2H). The quenched mixture was stirred for another hour which was followed by extraction with methylene chloride The organic layer was washed with brine was dried over anhydrous magnesium sulfate The magnesium sulfate was filtered off the filtrate was concentrated in vacuo The resulting residue was purified by recrystallization from hexane/dichloromethane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 68 ml thioanisole in 600 ml dichloromethane at 0° C., were added slowly in a series aluminum chloride (77.3 g) and (3-fluorophenyl)acetyl chloride (100 g). The reaction mixture was stirred for an hour, after which 1 L of aqueous HCl was added slowly to the reaction mixture. The quenched mixture was stirred for another hour, which was followed by extraction with methylene chloride. The organic layer was washed with brine and then was dried over anhydrous magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resulting residue was purified by recrystallization from hexane/dichloromethane to yield 142.9 g of 2-(3-fluorophenyl)-1-{4-(methylthio)-phenyl}-ethanone. mp: 94.5-95.5° C. NMR: δ2.52 (s, 3H), 4.23 (s, 2H), 6.95-7.05 (m, 3H),7.25-7.30 (m, 3H), 7.92 (d, J=8.7 Hz, 2H). The quenched mixture was stirred for another hour which was followed by extraction with methylene chloride The organic layer was washed with brine was dried over anhydrous magnesium sulfate The magnesium sulfate was filtered off the filtrate was concentrated in vacuo The resulting residue was purified by recrystallization from hexane/dichloromethane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 68 ml thioanisole in 600 ml dichloromethane at 0° C., were added slowly in a series aluminum chloride (77.3 g) and (3-fluorophenyl)acetyl chloride (100 g). The reaction mixture was stirred for an hour, after which 1 L of aqueous HCl was added slowly to the reaction mixture. The quenched mixture was stirred for another hour, which was followed by extraction with methylene chloride. The organic layer was washed with brine and then was dried over anhydrous magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resulting residue was purified by recrystallization from hexane/dichloromethane to yield 142.9 g of 2-(3-fluorophenyl)-1-{4-(methylthio)-phenyl}-ethanone. mp: 94.5-95.5° C. NMR: δ2.52 (s, 3H), 4.23 (s, 2H), 6.95-7.05 (m, 3H),7.25-7.30 (m, 3H), 7.92 (d, J=8.7 Hz, 2H). The quenched mixture was stirred for another hour which was followed by extraction with methylene chloride The organic layer was washed with brine was dried over anhydrous magnesium sulfate The magnesium sulfate was filtered off the filtrate was concentrated in vacuo The resulting residue was purified by recrystallization from hexane/dichloromethane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(3-Fluorophenyl)-acetyl]-5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (114) was synthesized from 5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (107) and (3-fluorophenyl)-acetyl chloride following the procedure described in Example 32. Reaction Conditions: 1,2-dichloroethane/RT. Purification: recrystallization from ether/pentane. Yield: 78%. 1H (CDCl3, 400 MHz): δ 10.6 (NH, broad s), 7.30 (1H, s), 7.26 (1H, dd), 7.04 (1H, d), 6.99 (1H, d), 6.92 (1H, dd), 4.37 (2H, q), 4.07 (2H, s), 2.58 (3H, s), 1.39 (3H, t) ppm. 13C (CDCl3, 100 MHz): δ 193.5, 164.0, 141.0, 137.4, 130.0, 125.3, 121.5, 120.5, 116.9, 116.4, 113.7, 61.0, 46.4, 14.4, 14.0 ppm. LC/MS: 98%. Reaction Conditions Purification recrystallization from ether/pentane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(3-Fluorophenyl)-acetyl]-3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester was synthesized from 3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (84) and (3-Fluorophenyl)-acetyl chloride following the procedure described in Example 32. Crude yield: 93%. 1H-NMR (400 MHz, CDCl3): δ 1.37 (t, 3H), 2.61 (s, 3H), 4.03 (s, 2H), 4.35 (q, 2H), 7.00 (m, 3H), 7.27 (m, 1H), 7.49 (d, 1H), 9.57 (s broad, 1H) ppm. 13C-NMR (100 MHz, CDCl3): □ 11.76, 14.38, 46.93, 60.84, 113.64, 116.30, 125.13, 127.17, 129.94, 137.42, 161.64, 193.02 ppm. DEPT (100 MHz, CDCl3): CH3 carbons: 11.76, 14.38; CH2 carbons: 46.93, 60.84; CH carbons: 116.30, 125.13, 127.17, 129.94 ppm. LC/MS: 91.29%, m/z=289.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(3-Fluorophenyl)-acetyl]-5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (114) was synthesized from 5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (107) and (3-fluorophenyl)-acetyl chloride following the procedure described in Example 32. Reaction Conditions: 1,2-dichloroethane/RT. Purification: recrystallization from ether/pentane. Yield: 78%. 1H (CDCl3, 400 MHz): δ 10.6 (NH, broad s), 7.30 (1H, s), 7.26 (1H, dd), 7.04 (1H, d), 6.99 (1H, d), 6.92 (1H, dd), 4.37 (2H, q), 4.07 (2H, s), 2.58 (3H, s), 1.39 (3H, t) ppm. 13C (CDCl3, 100 MHz): δ 193.5, 164.0, 161.6, 141.0, 137.4, 130.0, 125.3, 121.5, 120.5, 116.9, 116.4, 113.7, 61.0, 46.4, 14.4, 14.0 ppm. LC/MS: 98%. Reaction Conditions Purification recrystallization from ether/pentane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(3-Fluorophenyl)-acetyl]-3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester was synthesized from 3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (84) and (3-Fluorophenyl)-acetyl chloride following the procedure described in Example 32. Crude yield: 93%. 1H-NMR (400 MHz, CDCl3): δ 1.37 (t, 3H), 2.61 (s, 3H), 4.03 (s, 2H), 4.35 (q, 2H), 7.00 (m, 3H), 7.27 (m, 1H), 7.49 (d, 1H), 9.57 (s broad, 1H) ppm. 13C-NMR (100 MHz, CDCl3): □□□11.76, 14.38, 46.93, 60.84, 113.64, 116.30, 125.13, 127.17, 129.94, 137.42, 161.64, 193.02 ppm. DEPT (100 MHz, CDCl3): CH3 carbons: 11.76, 14.38; CH2 carbons: 46.93, 60.84; CH carbons: 116.30, 125.13, 127.17, 129.94 ppm. LC/MS: 91.29%, m/z=289.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(3-Fluorophenyl)-acetyl]-5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (114) was synthesized from 5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (107) and (3-fluorophenyl)-acetyl chloride following the procedure described in Example 32. Reaction Conditions: 1,2-dichloroethane/RT. Purification: recrystallization from ether/pentane. Yield: 78%. 1H (CDCl3, 400 MHz): δ 10.6 (NH, broad s), 7.30 (1H, s), 7.26 (1H, dd), 7.04 (1H, d), 6.99 (1H, d), 6.92 (1H, dd), 4.37 (2H, q), 4.07 (2H, s), 2.58 (3H, s), 1.39 (3H, t) ppm. 13C (CDCl3, 100 MHz): δ 193.5, 164.0, 161.6, 141.0, 137.4, 130.0, 125.3, 121.5, 120.5, 116.9, 116.4, 113.7, 61.0, 46.4, 14.4, 14.0 ppm. LC/MS: 98%. Reaction Conditions Purification recrystallization from ether/pentane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(3-Fluorophenyl)-acetyl]-3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester was synthesized from 3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (84) and (3-Fluorophenyl)-acetyl chloride following the procedure described in Example 32. Crude yield: 93%. 1H-NMR (400 MHz, CDCl3): δ 1.37 (t, 3H), 2.61 (s, 3H), 4.03 (s, 2H), 4.35 (q, 2H), 7.00 (m, 3H), 7.27 (m, 1H), 7.49 (d, 1H), 9.57 (s broad, 1H) ppm. 13C-NMR (100 MHz, CDCl3): □□□ 11.76, 14.38, 46.93, 60.84, 113.64, 116.30, 125.13, 127.17, 129.94, 137.42, 161.64, 193.02 ppm. DEPT (100 MHz, CDCl3): CH3 carbons: 11.76, 14.38; CH2 carbons: 46.93, 60.84; CH carbons: 116.30, 125.13, 127.17, 129.94 ppm. LC/MS: 91.29%, m/z=289.