Sulfuric Acid → N-(2-fluoro-5-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide

Participants

Reaction Steps

To N-(2-fluoro-5-aminophenyl)-3,4,5,6-tetrahydrophthalimide (VIII) (2.6 g), acetic acid (26 g) and conc. sulfuric acid (2.5 g) were added, and the resultant mixture was kept at a temperature below 10° C. A solution of sodium nitrite (1.0 g) in water (10 g) was added dropwise thereto at a temperature of 5° to 10° C. The resulting mixture was stirred for 15 minutes, followed by decomposition of excess of sodium nitrite with urea (0.3 g). A solution of cupric nitrate (38.6 g) in water (100 g) was added dropwise thereto at room temperature. After addition of cuprous oxide (1.5 g), the resultant mixture was stirred vigorously at room temperature for 10 minutes. The reaction mixture was extracted with ethyl acetate, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel chromatography using a mixture of n-hexane and ethyl acetate as an eluent to give 0.7 g of N-(2-fluoro-5-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide (VI). M.P., 164.6° C. M.P., 164.6° C.

Provenance & Evidence