3-(4-bromophenyl)propanoyl chloride

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

Procedure: To a solution of morpholine (11 g, 126.44 mmol, 2.01 equiv) in dichloromethane (60 mL) 0˜5° C. was added a solution of 3-(4-bromophenyl)propanoyl chloride (15.5 g, 63.01 mmol, 1.00 equiv) in dichloromethane (30 mL) dropwise with stirring. The resulting solution was stirred at 0˜5° C. for 1 h. The reaction mixture was warmed to room temperature. The resulting solution was diluted with 40 mL of water. The mixture was extracted with dichloromethane 2×100 mL. The combined organic layers was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 17.4 g (93%) of 3-(4-bromophenyl)-1-morpholinopropan-1-one as a white solid. The resulting solution was stirred at 0˜5° C. for 1 h The mixture was extracted with dichloromethane 2×100 mL The combined organic layers was washed with 3×50 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: To a solution of morpholine (11 g, 126.44 mmol, 2.01 equiv) in dichloromethane (60 mL) 0˜5° C. was added a solution of 3-(4-bromophenyl)propanoyl chloride (15.5 g, 63.01 mmol, 1.00 equiv) in dichloromethane (30 mL) dropwise with stirring. The resulting solution was stirred at 0˜5° C. for 1 h. The reaction mixture was warmed to room temperature. The resulting solution was diluted with 40 mL of water. The mixture was extracted with dichloromethane 2×100 mL. The combined organic layers was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 17.4 g (93%) of 3-(4-bromophenyl)-1-morpholinopropan-1-one as a white solid. The resulting solution was stirred at 0˜5° C. for 1 h The mixture was extracted with dichloromethane 2×100 mL The combined organic layers was washed with 3×50 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: A solution of 3-(4-bromophenyl)propanoic acid (14.5 g, 63.60 mmol, 1.00 equiv) in thionyl chloride (80 mL) was refluxed for 2 h. The reaction mixture was cooled to room temperature and then concentrated under vacuum to give 15.5 g (99%) of 3-(4-bromophenyl)propanoyl chloride as a light yellow oil. concentrated under vacuum

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(4-Bromophenyl)propionyl chloride (36.9 g, 0.15 mol) was dissolved in 300 mL DCM and AlCl3 (23.76 g, 0.18 mol) was added slowly. At the completion of the reaction, the mixture was heated to 40° C. and refluxed for 90 minutes and then poured onto ice. Dilute HCl aqueous solution was added and the mixture was extracted with diethyl ether. The organic layer was washed with 2M HCl aqueous solution, water and brine. The product was purified by column chromatography on silica gel eluting with PE:EA (20:1) to obtain a pale brown solid. After removing solvent under vacuum, 23 g (75%) of the desired product 6-bromo-2,3-dihydro-1H-inden-1-one (1B): 1H NMR (DMSO-d6, 400 MHz) δ2.6 (m, 2H), 3.1 (m, 2H), 7.55 (m, 1H), 7.1 (m, 1H), 7.85 (m, 1H). At the completion of the reaction refluxed for 90 minutes poured onto ice the mixture was extracted with diethyl ether The organic layer was washed with 2M HCl aqueous solution, water and brine The product was purified by column chromatography on silica gel eluting with PE EA (20:1) to obtain a pale brown solid After removing solvent under vacuum, 23 g (75%) of the desired product 6-bromo-2,3-dihydro-1H-inden-1-one (1B)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(4-Bromophenyl)propionyl chloride (36.9 g, 0.15 mol) was dissolved in 300 mL DCM and AlCl3 (23.76 g, 0.18 mol) was added slowly. At the completion of the reaction, the mixture was heated to 40° C. and refluxed for 90 minutes and then poured onto ice. Dilute HCl aqueous solution was added and the mixture was extracted with diethyl ether. The organic layer was washed with 2M HCl aqueous solution, water and brine. The product was purified by column chromatography on silica gel eluting with PE:EA (20:1) to obtain a pale brown solid. After removing solvent under vacuum, 23 g (75%) of the desired product 6-bromo-2,3-dihydro-1H-inden-1-one (1B): 1H NMR (DMSO-d6, 400 MHz) δ2.6 (m, 2H), 3.1 (m, 2H), 7.55 (m, 1H), 7.1 (m, 1H), 7.85 (m, 1H). At the completion of the reaction refluxed for 90 minutes poured onto ice the mixture was extracted with diethyl ether The organic layer was washed with 2M HCl aqueous solution, water and brine The product was purified by column chromatography on silica gel eluting with PE EA (20:1) to obtain a pale brown solid After removing solvent under vacuum, 23 g (75%) of the desired product 6-bromo-2,3-dihydro-1H-inden-1-one (1B)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(4-Bromophenyl)propionyl chloride (36.9 g, 0.15 mol) was dissolved in 300 mL DCM and AlCl3 (23.76 g, 0.18 mol) was added slowly. At the completion of the reaction, the mixture was heated to 40° C. and refluxed for 90 minutes and then poured onto ice. Dilute HCl aqueous solution was added and the mixture was extracted with diethyl ether. The organic layer was washed with 2M HCl aqueous solution, water and brine. The product was purified by column chromatography on silica gel eluting with PE:EA (20:1) to obtain a pale brown solid. After removing solvent under vacuum, 23 g (75%) of the desired product 6-bromo-2,3-dihydro-1H-inden-1-one (1B): 1H NMR (DMSO-d6, 400 MHz) δ2.6 (m, 2H), 3.1 (m, 2H), 7.55 (m, 1H), 7.1 (m, 1H), 7.85 (m, 1H). At the completion of the reaction refluxed for 90 minutes poured onto ice the mixture was extracted with diethyl ether The organic layer was washed with 2M HCl aqueous solution, water and brine The product was purified by column chromatography on silica gel eluting with PE EA (20:1) to obtain a pale brown solid After removing solvent under vacuum, 23 g (75%) of the desired product 6-bromo-2,3-dihydro-1H-inden-1-one (1B)

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

Procedure: To a solution of morpholine (11 g, 126.44 mmol, 2.01 equiv) in dichloromethane (60 mL) 0˜5° C. was added a solution of 3-(4-bromophenyl)propanoyl chloride (15.5 g, 63.01 mmol, 1.00 equiv) in dichloromethane (30 mL) dropwise with stirring. The resulting solution was stirred at 0˜5° C. for 1 h. The reaction mixture was warmed to room temperature. The resulting solution was diluted with 40 mL of water. The mixture was extracted with dichloromethane 2×100 mL. The combined organic layers was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 17.4 g (93%) of 3-(4-bromophenyl)-1-morpholinopropan-1-one as a white solid. The resulting solution was stirred at 0˜5° C. for 1 h The mixture was extracted with dichloromethane 2×100 mL The combined organic layers was washed with 3×50 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: A solution of 3-(4-bromophenyl)propanoic acid (14.5 g, 63.60 mmol, 1.00 equiv) in thionyl chloride (80 mL) was refluxed for 2 h. The reaction mixture was cooled to room temperature and then concentrated under vacuum to give 15.5 g (99%) of 3-(4-bromophenyl)propanoyl chloride as a light yellow oil. concentrated under vacuum

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

Procedure: To a solution of morpholine (11 g, 126.44 mmol, 2.01 equiv) in dichloromethane (60 mL) 0˜5° C. was added a solution of 3-(4-bromophenyl)propanoyl chloride (15.5 g, 63.01 mmol, 1.00 equiv) in dichloromethane (30 mL) dropwise with stirring. The resulting solution was stirred at 0˜5° C. for 1 h. The reaction mixture was warmed to room temperature. The resulting solution was diluted with 40 mL of water. The mixture was extracted with dichloromethane 2×100 mL. The combined organic layers was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 17.4 g (93%) of 3-(4-bromophenyl)-1-morpholinopropan-1-one as a white solid. The resulting solution was stirred at 0˜5° C. for 1 h The mixture was extracted with dichloromethane 2×100 mL The combined organic layers was washed with 3×50 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: A solution of 3-(4-bromophenyl)propanoic acid (14.5 g, 63.60 mmol, 1.00 equiv) in thionyl chloride (80 mL) was refluxed for 2 h. The reaction mixture was cooled to room temperature and then concentrated under vacuum to give 15.5 g (99%) of 3-(4-bromophenyl)propanoyl chloride as a light yellow oil. concentrated under vacuum