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

Temperature

35 °C

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)

1. additionafter the bleach addition
2. customthe reaction to completion
3. additionare added
4. temperatureAfter cooling at room temperature
5. customthe reaction is quenched by addition of saturated aqueous Na2SO3 (5 mL)
6. additionThe pH is adjusted to 8-9 by addition of NaOH 2M
7. washthe mixture is washed with ethyl acetate (2×)
8. customThe desired product is crystallized in the aqueous phase as a white solid (537 mg, 70%)

ORD record

ord-40f79e447a7f4750a12566dbf35335b5

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093402B2