Reacción #60293

Ecuación de reacción

6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde

lithiomethyl ethyl ether

4,4′-di-tert-butylbiphenyl

EtOCH2Cl

→

desired product

Rendimiento 44.0%

1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-ethoxy-ethanol

Rendimiento 44.0%

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroquenched with saturated aqueous NH4Cl at −78° C.
2. 2
   Extracciónextracted with EtOAc
3. 3
   LavadoThe organic layer is washed with brine
4. 4
   Secadodried over MgSO4
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated in vacuo
7. 7
   Otropurified by flash chromatography (100% CH2Cl2 to 3% to 5% MeOH in CH2Cl2)

Procedimiento

To a solution of lithiomethyl ethyl ether in THF (6 mL) (prepared from 4,4′-di-tert-butylbiphenyl (585 mg, 2.20 mmol), Li (18 mg, 2.59 mmol), and EtOCH2Cl (0.20 mL, 2.05 mmol) by the procedure reported in Tetrahedron 1996, 52, 1643) is added a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (29 mg, 0.080 mmol) in THF (1 mL) at −78° C. The resulting solution is stirred for 1 hour and then quenched with saturated aqueous NH4Cl at −78° C., warmed to room temperature, and extracted with EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (100% CH2Cl2 to 3% to 5% MeOH in CH2Cl2) to give the desired product (15 mg, 44%): MS APCI (+) m/z 428, 430 (M+, Br pattern) detected.

Fuente