反应详情

(S)-Benzyl 4-(3-amino-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (750 mg, 2.36 mmol) (Preparation E, Step D) was dissolved in toluene (20 mL). Racemic Binap (147 mg, 0.236 mmol), 1-bromo-2-fluoro-5-methyl-4-(methylsulfonyl)benzene (947 mg, 3.54 mmol) and Cs2CO3 (924 mg, 2.84 mmol) were added and the reaction was bubbled through with nitrogen for 5 minutes. Pd2 dba3 (108 mg, 0.118 mmol) was added and the reaction plunged into 95° C. oil bath overnight. The reaction was cooled to ambient temperature, filtered and concentrated. The residue was purified over silica gel (50 to 100% EtOAc in hexanes) to afford (S)-benzyl 4-(3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (906 mg, 1.80 mmol, 76.1% yield) as a tan solid.

1. customthe reaction was bubbled through with nitrogen for 5 minutes
2. customplunged into 95° C.
3. customovernight
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified over silica gel (50 to 100% EtOAc in hexanes)