Tempo → 2-(7-Fluoro-1H-1,3-benzodiazol-1-yl)acetic acid

Participants

Reaction Conditions

Reaction Steps

2-(7-fluoro-1H-benzimidazol-1-yl)ethanol (706 mg, 3.92 mmol) is suspended in 20 mL of acetonitrile and 15 mL of sodium phosphate buffer 1M (pH 6.5). The mixture is heated to 35° C. TEMPO (43 mg, 0.27 mmol) is added, followed by NaClO2 (80%, 887 mg, 7.84 mmol) dissolved in 4 mL of water and diluted bleach (2 ml of a 0.4% aqueous solution). The reaction mixture turns red-brown after the bleach addition. To drive the reaction to completion, if needed, more TEMPO (22 mg), NaClO2 (440 mg in 2 mL of water) and diluted bleach (1 mL) are added and the mixture stirred 6 hours at 35° C. After cooling at room temperature, the reaction is quenched by addition of saturated aqueous Na2SO3 (5 mL). The brown-red color disappears. The pH is adjusted to 8-9 by addition of NaOH 2M and the mixture is washed with ethyl acetate (2×). The organic layer is discarded and the aqueous phase is acidified with HCl 1M (up to pH 3). The desired product is crystallized in the aqueous phase as a white solid (537 mg, 70%). TLC: dichloromethane/methanol 10:1+5% triethylamine, Rf=0.33 (s.m.: Rf=0.56)

Provenance & Evidence