Reacción #52115

Ecuación de reacción

Lithium bis(trimethylsilyl)amide

(2S,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-imidazolidin-4-one

4-trifluoromethoxybenzyl bromide

→

(2R,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-5-(4-trifluoromethoxy-benzyl)-imidazolidin-4-one

Rendimiento 87.0%

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe mixture was stirred at −20° C. for 45 min
2. 2
   Temperaturawarmed to −5° C. over 1 h
3. 3
   ExtracciónThe resulting mixture was extracted with two portions of EtOAc (200,100 mL)
4. 4
   LavadoThe combined organic phases were washed with brine
5. 5
   Secadodried over Na2SO4
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated
8. 8
   OtroThe crude product was triturated with hexanes

Procedimiento

Lithium bis(trimethylsilyl)amide (LiHMDS) (38.0 mL, 1 M in THF) was added slowly dropwise over 25 min to a solution of (2S,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-imidazolidin-4-one (10.0 g, 25.17 mmol) in 60 mL of THF at −20° C. After stirring at −20° C. for 20 min, a solution of 4-trifluoromethoxybenzyl bromide (6.04 mL, 37.76 mmol) in 30 mL of THF was added dropwise over 20 min. The mixture was stirred at −20° C. for 45 min, warmed to −5° C. over 1 h, and then poured over 50 mL of ice-cold saturated NH4Cl solution. The resulting mixture was extracted with two portions of EtOAc (200,100 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was triturated with hexanes to afford 12.5 g (87%) of (2R,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-5-(4-trifluoromethoxy-benzyl)-imidazolidin-4-one as an off-white solid.

Fuente