Diisopropylethylamine → 2-(2-Iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

A 100 mL round bottom flask is charged with 2-iodo-3-methylbenzoic acid (1.92 g, 7.31 mmol) and dry DCM (25 mL). A stirring bar is added and stirring is initiated. After 5 min, the HBTU (2.37 g, 7.31 mmol) is added. After 5 min, the 2-amino-indane-2-carboxylic acid ethyl ester (1.5 g, 7.31 mmol) is added followed by N,N-diisopropylethyl-amine (3.2 mL, 18.37 mmol). The reaction is allowed to stir for 118 h. Analysis by tlc of the reaction mixture (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 (70 mL). This is washed dilute aqueous HCl (3%, 2×30 mL), saturated aqueous NaHCO3 (2×30 mL) and brine (30 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 2.04 g of a white solid. This material is dissolved in 15 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 10 column volumes. 27 mL fractions of UV active eluent are collected. Fractions 10 through 15 are combined and evaporated in vacuo. Pumping to constant weight gives 1.04 g a white solid material.

1. additionA stirring bar is added
2. waitAfter 5 min
3. stirringto stir for 118 h
4. customconsumption of the starting amine
5. customThe contents of the reaction flask are transferred to a separatory funnel
6. additiondiluted with EtOAc (70 mL)
7. washThis is washed dilute aqueous HCl (3%, 2×30 mL), saturated aqueous NaHCO3 (2×30 mL) and brine (30 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. customevaporated in vacuo

ORD record

ord-e32bebfa0fcf4686910bb7c3e06f3e39

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569535B2