Reacción #159170

Ecuación de reacción

4-Difluoromethoxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

LiOH

2,4′-dibromoacetophenone

triethylamine

HCl

→

title compound

Rendimiento 94.0%

4-Difluoromethoxymethyl-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester

Rendimiento 94.0%

Disolventes

MeOH

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe MeOH was removed under reduced pressure
2. 2
   workup.ADDITIONThe aqueous solution was poured into a separatory funnel
3. 3
   Extracciónextracted with DCM (3×)
4. 4
   SecadoThe combined organics were dried over MgSO4
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in MeCN (4 mL)
8. 8
   workup.STIRRINGAfter stirring for 15 h
9. 9
   Otrothe solvent was removed
10. 10
    OtroThe crude residue was purified by silica column chromatography (10% to 35% EtOAc/Hex)

Procedimiento

4-Difluoromethoxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (398 mg, 1.29 mmol) was dissolved in MeOH (8 mL) and LiOH (1 M in H2O, 2 mL, 2 mmol) was added. After stirring at RT for 5 h, the MeOH was removed under reduced pressure. The aqueous solution was poured into a separatory funnel, diluted with 1 M HCl (2 mL, 2 mmol) and extracted with DCM (3×). The combined organics were dried over MgSO4, filtered and concentrated. The residue was dissolved in MeCN (4 mL) and treated with 2,4′-dibromoacetophenone (200 mg, 0.719 mmol), and triethylamine (0.100 mL, 0.719 mmol). After stirring for 15 h, the solvent was removed. The crude residue was purified by silica column chromatography (10% to 35% EtOAc/Hex) to afford the title compound (303 mg, 94%).

Fuente