反应详情

To a solution of (3R,4S)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (1-10) (0.170 g, 0.601 mmol) in dichloromethane (5.0 mL) was added 3-cyclohexyl-3-[(methylthio)methyl]-8-azoniabicyclo[3.2.1]octane chloride (3-6) (0.174 g, 0.601 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 0.173 g, 0.901 mmol), 1-hydroxyl-7-azabenzotriazole (HOAT, 0.082 g, 0.603 mmol), and diisopropylethylamine (0.105 mL, 0.601 mmol). The mixture was stirred at room temperature overnight, diluted with methylene chloride, washed with water and a saturated aqueous solution of NaHCO3. The organic phase was dried over anhydrous MgSO4, filtered, and concentrated. Purification of the crude residue by preparative TLC (90% methylene chloride, 9% methanol, 1% of a 40% of NH4OH aqueous soltion as eluent), followed by the addition of one equivalent HCl in ether to afford (3-7) as white solid (m/z (ES) 519 (MH+)).

1. washwashed with water
2. dry with materialThe organic phase was dried over anhydrous MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. customPurification of the crude residue by preparative TLC (90% methylene chloride, 9% methanol, 1% of a 40% of NH4OH aqueous soltion as eluent),