3-(4-fluorophenyl)propanoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of 3-(4-fluorophenyl)propionyl chloride (287.6 g, 1.5 mol) in dichloromethane (1.4 L) was added dropwise during 3 h to an ice-cold, mechanically stirred suspension of aluminum chloride (226.0 g, 1.7 mol, Aldrich) in dichloromethane (2.2 L) under nitrogen. The resulting yellowish-black solution was refluxed for 5 h and allowed to cool to room temperature. The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to a tan solid (229.1 g, 99%). The solid was recrystallized from dichloromethane-hexane to give 215.7 g (93%) of 6-fluoro-1-indanone as off-white crystals, m.p., 57°-59° C.; The resulting yellowish-black solution was refluxed for 5 h The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L) The organic layer was dried over anhydrous sodium sulfate filtered concentrated to a tan solid (229.1 g, 99%) The solid was recrystallized from dichloromethane-hexane

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

Procedure: A mixture of 3-(4-fluorophenyl)propionic acid (275.1 g, 1.6 mol) and thionyl chloride (300 mL, 4.1 mol) was heated to reflux for 3 h, cooled to room temperature and distilled under aspirator vacuum to give 287.6 g (96%) of 3-(4-fluorophenyl)propionyl chloride as a pale pink oil, b.p., 120°-122° C./15 mm Hg: was heated to reflux for 3 h distilled under aspirator vacuum

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

Procedure: A solution of 3-(4-fluorophenyl)propionyl chloride (287.6 g, 1.5 mol) in dichloromethane (1.4 L) was added dropwise during 3 h to an ice-cold, mechanically stirred suspension of aluminum chloride (226.0 g, 1.7 mol, Aldrich) in dichloromethane (2.2 L) under nitrogen. The resulting yellowish-black solution was refluxed for 5 h and allowed to cool to room temperature. The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to a tan solid (229.1 g, 99%). The solid was recrystallized from dichloromethane-hexane to give 215.7 g (93%) of 6-fluoro-1-indanone as off-white crystals, m.p., 57°-59° C.; NMR (DMSO-d6): d 7.36-7.66 (m, 3H, Ar), 2.65-2.72, 3.06-3.10 (2m's, 4H, 2XCH2). The resulting yellowish-black solution was refluxed for 5 h The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L) The organic layer was dried over anhydrous sodium sulfate filtered concentrated to a tan solid (229.1 g, 99%) The solid was recrystallized from dichloromethane-hexane

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

Procedure: A mixture of 3-(4-fluorophenyl)propionic acid (275.1 g, 1.6 mol) and thionyl chloride (300 mL, 4.1 mol) was heated to reflux for 3 h, cooled to room temperature and distilled under aspirator vacuum to give 287.6 g (96%) of 3-(4-fluorophenyl)propionyl chloride as a pale pink oil, b.p., 120°-122° C./15 mm Hg; IR (neat) 1793,1511 cm-1 ; NMR (DMSO-d6): d7.04-7.32 (m, 4H, Ar), 2.50-2.89 (m, 4H, 2XCH2). was heated to reflux for 3 h distilled under aspirator vacuum

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

Procedure: A mixture of 3-(4-fluorophenyl)propionic acid (275.1 g, 1.6 mol) and thionyl chloride (300 mL, 4.1 mol) was heated to reflux for 3 h, cooled to room temperature and distilled under aspirator vacuum to give 287.6 g (96%) of 3-(4-fluorophenyl)propionyl chloride as a pale pink oil, b.p., 120°-122° C./15 mm Hg; IR (neat) 1793,1511 cm-1 ; NMR (DMSO-d6): d7.04-7.32 (m, 4H, Ar), 2.50-2.89 (m, 4H, 2XCH2). was heated to reflux for 3 h distilled under aspirator vacuum

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

Procedure: A procedure similar to step 2 of Example 1 was used. 3-(4-fluoro-phenyl)-propionyl chloride prepared in the step 1 and methylphenyl ether were used as starting materials, and anhydrous AlCl3 was used as catalyst. The obtained product was a white solid in a yield of 100%, mp: 80-81 └. 1H-NMR (CDCl3, 400 MHz) δ: 3.05 (2H, t, J=7.84 Hz, ArH), 3.23 (2H, t, J=7.84 Hz, ArH), 3.87 (3H, s, OCH3), 6.92 (2H, d, J=8.68 Hz, ArH), 6.97 (2H, t, 3JFH=3JHH=8.72 Hz, ArH), 7.21 (2H, dd, 3JHH=8.68 Hz, 4JFH=5.60 Hz, ArH), 7.93 (2H, d, J=8.68 Hz, ArH); EI-MS m/e (%): 258.0 (M+, 27), 135.0 (100).

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

Procedure: A solution of 3-(4-fluorophenyl)propionyl chloride (287.6 g, 1.5 mol) in dichloromethane (1.4 L) was added dropwise during 3 h to an ice-cold, mechanically stirred suspension of aluminum chloride (226.0 g, 1.7 mol, Aldrich) in dichloromethane (2.2 L) under nitrogen. The resulting yellowish-black solution was refluxed for 5 h and allowed to cool to room temperature. The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to a tan solid (229.1 g, 99%). The solid was recrystallized from dichloromethane-hexane to give 215.7 g (93%) of 6-fluoro-1-indanone as off-white crystals, m.p., 57°-59° C.; The resulting yellowish-black solution was refluxed for 5 h The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L) The organic layer was dried over anhydrous sodium sulfate filtered concentrated to a tan solid (229.1 g, 99%) The solid was recrystallized from dichloromethane-hexane

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

Procedure: A mixture of 3-(4-fluorophenyl)propionic acid (275.1 g, 1.6 mol) and thionyl chloride (300 mL, 4.1 mol) was heated to reflux for 3 h, cooled to room temperature and distilled under aspirator vacuum to give 287.6 g (96%) of 3-(4-fluorophenyl)propionyl chloride as a pale pink oil, b.p., 120°-122° C./15 mm Hg: was heated to reflux for 3 h distilled under aspirator vacuum

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

Procedure: A mixture of 3-(4-fluorophenyl)propionic acid (275.1 g, 1.6 mol) and thionyl chloride (300 mL, 4.1 mol) was heated to reflux for 3 h, cooled to room temperature and distilled under aspirator vacuum to give 287.6 g (96%) of 3-(4-fluorophenyl)propionyl chloride as a pale pink oil, b.p., 120°-122° C./15 mm Hg: was heated to reflux for 3 h distilled under aspirator vacuum

Conditions: temp:0.00; pressure:0.00; stir: