24424-99-5

956828-47-0

The general procedure for the synthesis of tert-butyl (4-chloro-2-fluorophenyl)-carbamate from di-tert-butyl dicarbonate is as follows: Example 1: N-(4-chloro-2-fluorophenyl)-N-methyl-3-oxo-1H,3H-spiro[2-benzofuran-1,3'-pyrrolidine]-1'-carboxamide Step 1. Synthesis of tert-butyl tert-butyl (4-chloro-2-fluorophenyl)carbamate To a solution of 4-chloro-2-fluoroaniline (4.0 mL, 0.036 mol; Aldrich) in tetrahydrofuran (40 mL, 0.4 mol) was added slowly and dropwise 1.0 M lithium hexamethyldisilazide in tetrahydrofuran (72 mL) at 0 °C for 1 hour. After the reaction solution turned bright purple, it was warmed to room temperature and stirring was continued for 30 min. Subsequently, a tetrahydrofuran solution (20 mL, 0.2 mol) of di-tert-butyl dicarbonate (8.30 g, 0.0380 mol) was added dropwise over 10 minutes. The reaction mixture was stirred at room temperature for 35 min before the reaction was quenched with saturated ammonium chloride solution and diluted with ethyl acetate to separate the organic layer. The combined organic layers were dried with anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The residue was purified by combiflash fast column chromatography using a gradient elution with a hexane solution of 0-10% ethyl acetate to give 4.33 g of orange solid product in 48.9% yield.The LCMS assay showed [M + H]+ of 246.1.