5-chlorospiro[2H-isoindole-3,1'-cyclopropane]-1-one

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-bromo-5-chlorophenyl)cyclopropanamine (2 g, 8.1 mmol), Pd(dppf)Cl2 (0.2 g), DIPEA (3.1 g, 24.3 mmol) in DMF (20 mL) was stirred in an autoclave under 2 MPa of CO (g) at 130° C. for 16 hours. The reaction mixture was diluted with EtOAc (300 mL), and washed with brine. The organic layer was dried over anhy. Na2SO4, filtered, and concentrated under reduced pressure to give a crude product which was purified by chromatography to afford title compound (700 mg, yield 44.6%) as a yellow solid. MS: 193.8 (M+H+, 1C1). washed with brine The organic layer was dried over anhy Na2SO4, filtered concentrated under reduced pressure to give a crude product which was purified by chromatography

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-bromo-5-chlorophenyl)cyclopropanamine (2 g, 8.1 mmol), Pd(dppf)Cl2 (0.2 g), DIPEA (3.1 g, 24.3 mmol) in DMF (20 mL) was stirred in an autoclave under 2 MPa of CO (g) at 130° C. for 16 hours. The reaction mixture was diluted with EtOAc (300 mL), and washed with brine. The organic layer was dried over anhy. Na2SO4, filtered, and concentrated under reduced pressure to give a crude product which was purified by chromatography to afford title compound (700 mg, yield 44.6%) as a yellow solid. MS: 193.8 (M+H+, 1C1). washed with brine The organic layer was dried over anhy Na2SO4, filtered concentrated under reduced pressure to give a crude product which was purified by chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-chloro-2-cyanobenzoate (2.0 g, 10.2 mmol) in Et2O (40 mL) was added Ti(OiPr)4 (3.43 ml, 11.7 mmol). After cooling to 0° C., a 3.0 M solution of EtMgBr in Et2O (6.8 ml, 20.4 mmol) was added slowly. The reaction was warmed to room temperature and stirred for 3 h. Upon completion, the reaction was quenched with 1.0 M HCl (20 mL) then filtered over celite. The layers were separated and the aqueous layer was washed with EtOAc (2×20 mL). The combined organics were dried over Na2SO4, then filtered and concentrated. The crude product was purified by flash chromatography over silica gel (2-5% MeOH/DCM eluent) to provide 6′-chlorospiro[cyclopropane-1,1′-isoindolin]-3′-one (400 mg, 21% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.75 (br. s., 1H), 7.66 (d, J=8.5 Hz, 1H), 7.40-7.54 (m, 2H), 1.47 (dt, J=11.2, 2.8 Hz, 4H); MS m/z C10H8ClNO [M+1]+=194.6. The reaction was warmed to room temperature Upon completion, the reaction was quenched with 1.0 M HCl (20 mL) then filtered over celite The layers were separated the aqueous layer was washed with EtOAc (2×20 mL) The combined organics were dried over Na2SO4 filtered concentrated The crude product was purified by flash chromatography over silica gel (2-5% MeOH/DCM eluent)