反应详情

温度

-20 °C

To a solution of (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester (1.83 g, 8.07 mmol) in dry THF (45 mL) at −20° C. under nitrogen atmosphere was added triethylamine (3.32 mL, 23.8 mmol) followed by ethylchloroformate (0.775 mL, 8.07 mmol) dropwise. The reaction mixture was stirred at −20° C. for 90 min and a solution of 2-fluoro-3-(trifluoromethoxy)aniline (prepared as described in Part C, 1.5 g, 7.69 mmol) in dry THF (5 mL) was added. The reaction mixture was further stirred at −20° C. for 1 h, warmed up to RT and stirred at 65° C. for 16 h until completion of the reaction. The reaction mixture was diluted with EtOAC, washed with a saturated aqueous solution of NaHCO3 (×3) and brine, dried (phase separator) and concentrated under reduced pressure. The crude residue was purified via flash column chromatography on silica gel (EtOAc/c-hexane 1:1) to give the desired material as a colorless oil. MS: 427 [M+Na]+, 304.9 [MH−Boc]+; tR (HPLC conditions c): 5.23 min.

1. stirringThe reaction mixture was further stirred at −20° C. for 1 h
2. temperaturewarmed up to RT
3. stirringstirred at 65° C. for 16 h until completion of the reaction
4. additionThe reaction mixture was diluted with EtOAC
5. washwashed with a saturated aqueous solution of NaHCO3 (×3) and brine
6. customdried (phase separator)
7. concentrationconcentrated under reduced pressure
8. customThe crude residue was purified via flash column chromatography on silica gel (EtOAc/c-hexane 1:1)