反应详情

To a solution of tert-butyl 3-cyano-3-fluoropyrrolidine-1-carboxylate (240 mg, 1.12 mmol) in CH2Cl2 (5 mL) was added TFA (2.0 mL, 26.0 mmol). The pale yellow reaction mixture was stirred at room temperature for 4 h then concentrated to a yellow oil and dried under high vacuum. In a 50 mL flask were combined the above oil (237 mg, 1.04 mmol), (R)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (200 mg, 0.87 mmol), and HOBT (146 mg, 0.95 mmol). Then added DMF (4 mL) followed by HATU (362 mg, 0.95 mmol) and N,N-diisopropylethylamine (0.45 mL, 2.59 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with H2O and extracted with EtOAc (3×). The combined organics were washed with H2O (3×) then dried over MgSO4 and concentrated. The crude residue was purified by SiO2 chromatography (20% to 50% EtOAc/hexanes) to isolate 234 mg (83%) of tert-butyl (2R)-1-(3-cyano-3-fluoropyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate as a viscous colorless oil.

1. concentrationthen concentrated to a yellow oil
2. customdried under high vacuum
3. customIn a 50 mL flask were combined
4. stirringThe yellow reaction mixture was stirred at room temperature overnight
5. customthen quenched with H2O
6. extractionextracted with EtOAc (3×)
7. washThe combined organics were washed with H2O (3×)
8. dry with materialthen dried over MgSO4
9. concentrationconcentrated
10. customThe crude residue was purified by SiO2 chromatography (20% to 50% EtOAc/hexanes)