Yield:-

Reaction Conditions:

with trifluorormethanesulfonic acid at 100; for 24 h;

Steps:

56; 57

Reference Example 56 and Reference Example 57; 7-Chloro-6-fluoro-2,2-dimethylindan-1-one, and 5-Chloro-6-fluoro-2,2-dimethylindan-1-one; 3-(3-Chloro-4-fluorophenyl)propionic acid (9.8 g) was dissolved in TFOH (40 ml), followed by stirring in an argon atmosphere at 100°C for 24 hours. The reaction solution was poured into ice-water, extracted with diethyl ether, and washed with saturated sodium hydrogencarbonate, and saturated brine. Then, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 10/1 to 3/1) to obtain a mixture (7.2 g) of 5-chloro-6-fluoroindan-1-one and 7-chloro-6-fluoroindan-1-one. Then, this was dissolved in THF (200 ml), MeI (6.1 ml) was added thereto, and with stirring at room temperature, 55% oily NaH (4.3 g) was added thereto gradually with taking 30 minutes. After the heat generation stopped, an aqueous saturated ammonium chloride solution was added to the reaction solution, followed by extraction with diethyl ether, and washing with saturated brine. This was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 30/1 to 10/1) to obtain the compound (0.85 g) of Reference Example 56 and the compound (5.9 g) of Reference Example 57.

References:

EP1795524,2007,A1 Location in patent:Page/Page column 23