7-chloro-1-(2-fluorophenyl)heptan-1-one

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

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

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: Prepared by Procedure K and Scheme E using K2CO3 instead of Na2CO3 and NaI instead of KI and 7-chloro-1-(2-fluorophenyl)-1-heptanone and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: 1H NMR (400 MHz, CDCl3), δ 8.17 (s, br, 1H), 8.06-6.88 (m, 8H), 3.08-2.94 (m, 4H), 2.62-2.48 (m, 1H), 2.48-2.38 (m, 1H) 2.38-2.15 (m, 2H), 2.02-1.92 (m, 2H), 1.84-1.77 (m, 4H), 1.77-1.66 (m, 2H), 1.62-1.46 (m, 2H), 1.46-1.29 (M, 4H), 1.21 (d, 6H, J=6.8 Hz); ESMS m/e: 453.2 (M+H)+. Prepared by Procedure K and Scheme E

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50-mL round-bottom flask was charged with a solution of 7-chloro-1-oxo-1(2-fluorophenyl)heptane (2.42 g, 10.0 mmol), 2-methyl-N-[3-(4-piperidyl)phenyl]propanamide (2.46 g, 10.0 mmol), K2CO3 (2.76 g, 20.0 mmol) and NaI (2.25 g, 15.0 mmol) in DMF (25.0 mL). The mixture was stirred for 10 min at 25° C. and then heated at 100° C. for 12 h, cooled to 25° C. and diluted with EtOAc (100 mL) The reaction mixture was washed with water (4×50 mL) and the aqueous layer was extracted with EtOAc (100 mL). The organic layers were washed with brine (50 mL), dried over MgSO4, concentrated in vacuo and the crude product was purified by chromatography (EtOAc:MeOH 97:3) to give the desired product (3.70 g, 82.0%). heated at 100° C. for 12 h cooled to 25° C. was washed with water (4×50 mL) the aqueous layer was extracted with EtOAc (100 mL) The organic layers were washed with brine (50 mL) dried over MgSO4 concentrated in vacuo the crude product was purified by chromatography (EtOAc:MeOH 97:3)

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

Procedure: Prepared by Procedure K and Scheme E using K2CO3 instead of Na2CO3 and NaI instead of KI and 7-chloro-1-(2-fluorophenyl)-1-heptanone and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: 1H NMR (400 MHz, CDCl3), δ 8.17 (s, br, 1H), 8.06–6.88 (m, 8H), 3.08–2.94 (m, 4H), 2.62–2.48 (m, 1H), 2.48–2.38 (m, 1H), 2.38–2.15 (m, 2H), 2.02–1.92 (m, 2H), 1.84–1.77 (m, 4H), 1.77–1.66 (m, 2H), 1.62–1.46 (m, 2H), 1.46–1.29 (M, 4H), 1.21 (d, 6H, J=6.8 Hz); ESMS m/e: 453.2 (M+H)+. Prepared by Procedure K and Scheme E

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50-mL round-bottom flask was charged with a solution of 7-chloro-1-oxo-1(2-fluorophenyl)heptane (2.42 g, 10.0 mmol), 2-methyl-N-[3-(4-piperidyl)phenyl]propanamide (2.46 g, 10.0 mmol), K2CO3 (2.76 g, 20.0 mmol) and NaI (2.25 g, 15.0 mmol) in DMF (25.0 mL). The mixture was stirred for 10 min at 25° C. and then heated at 100° C. for 12 h, cooled to 25° C. and diluted with EtOAc (100 mL). The reaction mixture was washed with water (4×50 mL) and the aqueous layer was extracted with EtOAc (100 mL). The organic layers were washed with brine (50 mL), dried over MgSO4, concentrated in vacuo and the crude product was purified by chromatography (EtOAc:MeOH 97:3) to give the desired product (3.70 g, 82.0%). heated at 100° C. for 12 h cooled to 25° C. The reaction mixture was washed with water (4×50 mL) the aqueous layer was extracted with EtOAc (100 mL) The organic layers were washed with brine (50 mL) dried over MgSO4 concentrated in vacuo the crude product was purified by chromatography (EtOAc:MeOH 97:3)