Methyl 1-[(4-fluorophenyl)carbamoyl]cyclopropanecarboxylate

113020-21-6

371-40-4

1345847-71-3

Example B1: Cyclopropane-1,1-dicarboxylic acid monomethyl ester (2 g, 13.88 mmol) was dissolved in N,N-dimethylformamide (DMF, 28 mL), and 4-fluoroaniline (1.999 mL, 20.82 mmol), N,N-diisopropylethylamine (12.12 mL, 69.4 mmol), and O-(benzotriazol-1-yl)- N,N,N',N'-tetramethylurea tetrafluoroborate (TBTU, 8.91 g, 27.8 mmol). The reaction mixture was stirred at room temperature for 15 h. After completion of the reaction, the reaction solution was diluted with ethyl acetate (200 mL) and washed sequentially with 10% aqueous lithium chloride solution (3 x 100 mL) and saturated aqueous sodium chloride solution (100 mL). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a brown solid crude product. Purification by silica gel column chromatography (eluent: 0 to 20% ethyl acetate/hexane gradient elution) afforded methyl 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylate (3.28 g, 99% yield) as a light yellow solid. NMR hydrogen spectrum (400 MHz, DMSO-d6) δ: 10.32 (s, 1H), 7.60 (m, 2H), 7.12 (m, 2H), 3.66 (s, 3H), 1.38 (m, 4H); mass spectrum (ESI) m/z: 238.1 ([M+H]+).