(4-bromo-2-chlorophenyl)-pyrrolidin-1-ylmethanone

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

Procedure: 4-Bromo-2-chloro-benzoic acid (30 g, 127.4 mmol) was placed in a 3 L round bottom flask and 1.5 L of EtOAc was transferred into it. Triethylamine (25.8 g, 255 mmol), pyrrolidine (18 g, 255 mmol), and T3P (48.6 g, 152.9 mmol, 50 wt % in EtOAc) were then added. After 1 hr, the reaction was quenched with 200 mL of 1N NaOH and stirred for 10 min. The layers were separated and after 2 more extractions of the aqueous phase with EtOAc (2×500 ml), the combined organic extracts were dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to obtain a viscous oil. Flash chromatography using a 330 g ISCO™ column and 50%, 80% EtOAc/Hexanes yielded the title compound as a light yellow colored viscous oil (35.4 g, 96% yield). Rf=0.25 (50% EtOAc/Hexanes), LRMS m/z Calcd for C11H11BrClNO, 288.6, found, 289.9 (M+H) APCI; 1H-NMR (CDCl3) δ 7.56 (d, J=1.7 Hz, 1H), 7.43 (dd, J=1.7, 8.3 Hz, 1H), 7.17 (d, J=8.3 Hz, 1H), 3.63 (b apt t, J=6.6 Hz, 2H), 3.17 (B apt t, J=6.6 Hz, 2H), 2.00-1.84 (m, 4H). 13C-NMR (CDCl3) δ 166.0, 136.6, 132.6, 131.3, 130.7, 128.9, 123.3, 48.0, 45.8, 26.1, 24.7. the reaction was quenched with 200 mL of 1N NaOH The layers were separated after 2 more extractions of the aqueous phase with EtOAc (2×500 ml) the combined organic extracts were dried over MgSO4 filtered The filtrate was concentrated under reduced pressure to obtain a viscous oil

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

Procedure: 4-Bromo-2-chloro-benzoic acid (30 g, 127.4 mmol) was placed in a 3 L round bottom flask and 1.5 L of EtOAc was transferred into it. Triethylamine (25.8 g, 255 mmol), pyrrolidine (18 g, 255 mmol), and T3P (48.6 g, 152.9 mmol, 50 wt % in EtOAc) were then added. After 1 hr, the reaction was quenched with 200 mL of 1N NaOH and stirred for 10 min. The layers were separated and after 2 more extractions of the aqueous phase with EtOAc (2×500 ml), the combined organic extracts were dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to obtain a viscous oil. Flash chromatography using a 330 g ISCO™ column and 50%, 80% EtOAc/Hexanes yielded the title compound as a light yellow colored viscous oil (35.4 g. 96% yield) Rf=0.25 (50% EtOAc/Hexanes), LRMS m/z Calcd for C11H11BrClNO, 288.6, found, 289.9 (M+H) APCI; 1H-NMR (CDCl3) δ 7.56 (d, J=1.7 Hz, 1H), 7.43 (dd, J=1.7, 8.3 Hz, 1H) 7.17 (d, J=8.3 Hz, 1H), 3.63 (b apt t, J=6.6 Hz, 2H), 3.17 (B apt t, J=6.6 Hz, 2H), 2.00-1.84 (m, 4H). 13C-NMR (CDCl3) δ 166.0, 13.6, 132.6, 131.3, 130.7, 128.9, 123.3, 48.0, 45.8, 261, 24.7. the reaction was quenched with 200 mL of 1N NaOH The layers were separated after 2 more extractions of the aqueous phase with EtOAc (2×500 ml) the combined organic extracts were dried over MgSO4 filtered The filtrate was concentrated under reduced pressure to obtain a viscous oil