Synthesis
The general procedure for the synthesis of 1-indanone-6-carboxylic acid from 4-(2-carboxyethyl)benzoic acid is as follows: 6-carboxy-1-indanone, which is the feedstock of Example 206, was prepared as follows: 3-(4-carboxyphenyl)propionic acid (5 g, 0.026 mol), fresh AlCl3 (25 g, 7.2 equivalents, 0.187 mol) and NaCl (2.5 g , 10% of the mass of AlCl3) were added to a 100 mL flask equipped with a condenser and an internal thermometer. The flask was shaken briefly to mix the solids well and subsequently heated in an oil bath set at 190°C. The reaction was maintained at an internal temperature of 180°C or above for 1 hour (the mixture melted to a dark brown liquid during the reaction). After the reaction was complete, the mixture was cooled and poured into a 2000 mL beaker containing ice and washed with water. 180mL of 6M HCl and 250mL of EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc (3 x 200mL). The organic layers were combined, washed sequentially with 2M HCl, water and brine, dried with MgSO4, filtered and concentrated in vacuum to give a light brown solid 6-carboxy-1-indanone (4.10 g, 90% yield), which was used directly in the next synthesis.
References
[1] Patent: WO2005/87236, 2005, A1. Location in patent: Page/Page column 39
[2] Patent: US2010/249095, 2010, A1. Location in patent: Page/Page column 68-69
[3] Tetrahedron, 1995, vol. 51, # 1, p. 203 - 216
[4] Journal of the Chemical Society, 1956, p. 4647,3652
[5] Patent: US2012/71461, 2012, A1. Location in patent: Page/Page column 60
