反应详情

A 40 mL reaction vial is charged with 2-cyclobutoxyl-3-methyl-5-chloro-benzoic acid (221, 0.40 g, 1.62 mmol) and dry DCM (5 mL). A stirring bar is added. Stirring is initiated. After dissolution is complete, the HBTU (630 mg, 1.66 mmol) is added. After 5 min, the 2-amino-5-fluoro-indane-2-carboxylic acid ethyl ester. (19, 371 mg, 1.66 mmol is added followed by DIPEA (0.74 mL, 4.16 mmol). The reaction is allowed to stir for 5 days. Analysis by tlc of the reaction mixture (silica, 5% 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 (50 mL). This is washed consecutively with dilute aqueous HCl (3%, 20 mL), saturated aqueous NaHCO3 (20 mL) and brine (20 mL), and then dried over MgSO4, filtered and evaporated in vacuo to provide 1 g of light yellow oil. This material is dissolved in 10 mL of DCM. This material is purified utilizing an ISCO Companion with a 24 g cartridge of silica. The gradient is 10% EtOAc in heptanes over 4 column volumes followed by a linear gradient to 70% EtOAc in heptanes over 10 column volumes. 17 mL fractions are collected. Fractions 22 through 28 are combined and evaporated in vacuo by pumping to a constant weight to give white solid (0.65 g, 88%).

1. customA 40 mL reaction
2. additionA stirring bar is added
3. dissolutionAfter dissolution
4. addition(19, 371 mg, 1.66 mmol is added
5. stirringto stir for 5 days
6. customconsumption of the starting amine
7. customThe contents of the reaction flask are transferred to a separatory funnel
8. additiondiluted with EtOAc (50 mL)
9. washThis is washed consecutively with dilute aqueous HCl (3%, 20 mL), saturated aqueous NaHCO3 (20 mL) and brine (20 mL)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customevaporated in vacuo