2-chloro-3,4-difluorobenzonitrile

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

Procedure: A mixture of (2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidine 1/2 oxalate (639 mg), 2-chloro-3,4-difluorobenzonitrile (491 mg), lithium carbonate (669 mg) and dimethyl sulfoxide (13 mL) was stirred at 90° C. for 1 hr. The reaction mixture was cooled and partitioned between water and ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate-hexane). The obtained solid was recrystallized from ethyl acetate to give the title compound as crystals (yield: 538 mg). The reaction mixture was cooled partitioned between water and ethyl acetate The organic layer was washed with water dried over anhydrous sodium sulfate concentrated The obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate-hexane) The obtained solid was recrystallized from ethyl acetate

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

Procedure: To a mixture of 2-chloro-3,4-difluorobenzamide (1.20 g), pyridine (1.01 mL) and N,N-dimethylformamide (18 mL) was added oxalyl chloride (0.82 mL) at 0° C. over 10 min. The mixture was stirred for 1 hr while raising the temperature to room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate-hexane) to give the title compound as a solid (yield: 983 mg). extracted with ethyl acetate The organic layer was washed with water dried over anhydrous sodium sulfate concentrated The obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate-hexane)