methyl 3-chloro-2-cyanobenzoate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a slurry of ZnCl2 (0.77 mmol) in 5 mL THF was added LiBH4 (1.64 mmol, 2M in THF) at RT. After heating to 50° C. for 90 min, a solution of 3-chloro-2-cyanobenzoic acid methyl ester (0.81 mmol) in 5 mL THF was slowly added and the mixture was heated to 60° C. overnight. The reaction mixture was then cooled to 5° C., acidified with 2M HCl solution and extracted with EtOAc. The aq. phase was basified with 1M NaOH solution, extracted twice with EtOAc, dried over MgSO4 and concentrated in vacuo to give the desired product as yellowish oil. the mixture was heated to 60° C. overnight The reaction mixture was then cooled to 5° C. extracted with EtOAc extracted twice with EtOAc dried over MgSO4 concentrated in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-3-chlorobenzoic acid methyl ester (3.86 mmol) in 4 mL DMF was added CuCN (4.24 mmol) and the reaction mixture was heated to 90° C. overnight. After cooling to 10° C., 10 mL EtOAc and 3 mL 1M NaOH solution were added and stirring was continued at RT for 30 min. The aq. phase was separated and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification by preparative LC-MS (method L) gives the desired product as white solid. After cooling to 10° C. The aq. phase was separated extracted twice with EtOAc The combined organic layers were washed with brine dried over MgSO4 concentrated in vacuo Purification by preparative LC-MS (method L)