反应详情

A 30 mL reaction vial is charged with 2-aminoindan-2-carboxylic acid ethyl ester (1 g, 4.87 mmol) and dry DCM (5 mL). A stirring bar is added and stirring is initiated. DIPEA (1.35 mL, 7.8 mmol) is added. 2,5-dichloro-pyridine-3-carbonyl chloride (1.23 g, 5.85 mmol) and DMAP (8 mg, cat.) are added. The reaction is capped. After 57 days, tlc analysis (silica, 10% iPrOH/DCM) indicates that the starting has been completely consumed. The contents of the reaction flask are transferred to a separatory funnel and diluted with EtOAc (60 mL). This is washed with water (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL), and then dried over MgSO4, filtered and evaporated by pumping to constant weight yields 1.99 g of off-white solid. This is diluted with DCM (20 mL) and applied to a silica column ((80 g) on an ISCO Companion. The column is eluted with 5% EtOAc in heptanes for 3 column volumes followed by a linear gradient to 75% EtOAc in heptanes over 12 column volumes. 17 mL fractions of UV positive eluent are collected. Fraction 12-16 are combined and evaporated by pumping to constant weight to give light yellow solid (1.39 g, 75%).

1. customA 30 mL reaction
2. additionA stirring bar is added
3. customThe reaction is capped
4. customhas been completely consumed
5. customThe contents of the reaction flask are transferred to a separatory funnel
6. additiondiluted with EtOAc (60 mL)
7. washThis is washed with water (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. customevaporated