反应详情

A 30 mL vial is charged with 2-cyclobutoxy-3-methyl-benzoic acid (734 mg, 3.56 mmol) and dry DCM (10 mL). A stirring bar is added and stirring is initiated. After 5 min, HTBU (1.35 g, 3.56 mmol) is added. After 5 min, 2-amino-indane-2-carbonitrile. (308, 563 mg, 3.56 mmol) is added followed by DIPEA (1.5 mL, 8.95 mmol). The reaction is allowed to stir for 38 h. Analysis of the reaction mixture by tlc (silica, 15% iPrOH/DCM) indicates complete consumption of the starting amine. The contents of the reaction flask are transferred to a separatory funnel and diluted with EtOAc (60 mL). This is washed saturated aqueous NaHCO3 (2×20 mL) and brine (20 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 1.2 g of thick black oil. This material is dissolved in 10 mL of DCM. This material is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 10% EtOAc in heptanes over 4 column volumes followed by a linear gradient to 50% EtOAc over 8 column volumes and then 90% EtOAc in heptanes for 2 column volumes. 17 mL fractions of UV active eluent are collected. Fractions 27 through 30 are combined and evaporated in vacuo to give white solid (0.51 g, 41%).

1. additionA stirring bar is added
2. additionHTBU (1.35 g, 3.56 mmol) is added
3. waitAfter 5 min
4. addition(308, 563 mg, 3.56 mmol) is added
5. stirringto stir for 38 h
6. customconsumption of the starting amine
7. customThe contents of the reaction flask are transferred to a separatory funnel
8. additiondiluted with EtOAc (60 mL)
9. washThis is washed saturated aqueous NaHCO3 (2×20 mL) and brine (20 mL)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customevaporated in vacuo