Reacción #164047

Ecuación de reacción

LHMDS

3-chlorobenzonitrile

methyl cyanoformate

→

(2-chloro-4-cyanophenyl)acetic acid methyl ester

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONis added
2. 2
   workup.WAITthe solution is left at −78° C. for 2 h
3. 3
   OtroThe excess LHMDS is quenched with aqueous saturated NH4Cl
4. 4
   workup.ADDITIONThe mixture is then diluted with EtOAc
5. 5
   Lavadowashed with aqueous saturated NH4Cl (2×)
6. 6
   SecadoOrganic is dried (Na2SO4)
7. 7
   Otroevaporated
8. 8
   OtroThe crude residue is purified via flash column chromatography (EtOAc/hexanes 1:1→EtOAc)

Procedimiento

4-{5-[2-tert-Butyldimethylsilanyloxy)ethyl]imidazol-1-ylmethyl}-3-chlorobenzonitrile (1.7 g, 4.52 mmol) is dissolved in anhydrous THF (30 mL) and stirred at −78° C. before a THF solution of LHMDS (8.1 mL, 1.0 M) is added. After 15 min, methyl cyanoformate (0.38 mL, 4.74 mmol) is added and the solution is left at −78° C. for 2 h. The excess LHMDS is quenched with aqueous saturated NH4Cl and the mixture is allowed to warm to room temperature. The mixture is then diluted with EtOAc and washed with aqueous saturated NH4Cl (2×). Organic is dried (Na2SO4) and evaporated. The crude residue is purified via flash column chromatography (EtOAc/hexanes 1:1→EtOAc) to give {5-[2-tert-butyldimethylsilanyloxy)ethyl]-imidazol-1-yl}-(2-chloro-4-cyanophenyl)acetic acid methyl ester as an oil. MS (ESI) m/z 434.3, 436.3 (M+H).

Fuente