反应详情

A 40 mL reaction vial which contains a stirring bar is charged with 3-n-propoxypicolinic acid (397 mg, 2.19 mmol) and dry DCM (6 mL). Stirring is initiated. After 2 min, the HTBU (831 mg, 2.195 mmol) is added. After 5 min, the 2-amino)-indane-2-carboxylic acid ethyl ester (450 mg, 2.19 mmol is added followed by DIPEA (0.96 mL, 5.48 mmol). The reaction is allowed to stir at ambient temperature. After 20 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%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL), and dried over MgSO4, filtered and evaporated in vacuo to give 1.23 g of light orange solid. 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 3 column volumes followed by a linear gradient to 60% EtOAc in heptanes over 10 column volumes. 17 mL fractions eluent are collected. Fractions 57 through 67 are combined and evaporated in vacuo by pumping to constant weight to give white solid (0.8 g, 99%).

1. customA 40 mL reaction vial which
2. additionthe HTBU (831 mg, 2.195 mmol) is added
3. waitAfter 5 min
4. stirringto stir at ambient temperature
5. waitAfter 20 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%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customevaporated in vacuo
13. customto give 1.23 g of light orange solid
14. customThis material is purified
15. custom17 mL fractions eluent are collected
16. customevaporated in vacuo