methyl 4-chloro-2-cyanobenzoate

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)