Synthesis
Step E General procedure for the synthesis of 5-(trifluoromethyl)indan-1-one from 3-[2-bromo-5-(trifluoromethyl)phenyl]propionic acid: to a mixture of 3-[2-bromo-5-(trifluoromethyl)phenyl]propionic acid (2.8 g, 9.4 mmol) in THF (100 mL) and hexanes (20 mL) was added slowly and dropwise at -78°C a solution of 2.5 M n-butyllithium in hexane (8.3 mL). After dropwise addition, the reaction was quenched with saturated aqueous NH4Cl solution. The reaction mixture was extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4 and concentrated. The crude product was purified by fast column chromatography on silica gel with 10-20% EtOAc/hexane as eluent to afford the target product 5-(trifluoromethyl)indan-1-one as a white solid (0.7 g, 37% yield).LC/MS analysis: the calculated value of (M+H)+ for C10H7F3O was 201; measured value, 201.1.
References
[1] Patent: US2005/261310, 2005, A1. Location in patent: Page/Page column 25
[2] ACS Medicinal Chemistry Letters, 2010, vol. 1, # 9, p. 483 - 487
