1,1'-Carbonyldiimidazole → N-[[3,5-bis-(trifluoromethyl)phenyl]methyl]-3,4-dichloro-beta-(2-hydroxyethyl)-N-methyl-benzenepropanamide

3,4-Dichloro-β[2-[[3,5-bis-(trifluoromethyl)phenylmethyl]methylamino]-2-oxoethyl]-benzenepropanoic acid (6.1 g) in EtOAc (75 mL) was treated with carbonyldiimidazole (2.43 g) and N,N-dimethylaminopyridine (150 mg). The resulting solution was stirred at room temperature for 15 minutes and then heated at 50° C. for two hours. The reaction mixture was cooled to 0° C. and treated with a solution of NaBH4 (1.8 g) in H2O (30 mL), warmed slowly to room temperature and stirred for 12 hours. The reaction mixture was diluted with EtOAc (150 mL) and washed with 1N HCl (1×100 mL), sat. NaHCO3 (1×100 mL) and water (1×100 mL). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure to yield the crude compound as a oil. Silica gel chromatography eluting with 0-10% MeOH/CH2Cl2 gave the title compound (5.7 g). Mass spectrum (FAB): 502.0791.

1. temperatureheated at 50° C. for two hours
2. temperatureThe reaction mixture was cooled to 0° C.
3. temperaturewarmed slowly to room temperature
4. stirringstirred for 12 hours
5. washwashed with 1N HCl (1×100 mL), sat. NaHCO3 (1×100 mL) and water (1×100 mL)
6. dry with materialThe organic phase was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto yield the crude compound as a oil
10. washSilica gel chromatography eluting with 0-10% MeOH/CH2Cl2

ORD record

ord-b057f8a790764a6d8fa590917b14d426

Source dataset

uspto-grants-1997_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05654316