Step D: Synthesis of 6-(trifluoromethyl)-1-indanone
To a mixed solution of 3-(2-bromo-4-(trifluoromethyl)phenyl)propanoic acid (6.40 g, 21.5 mmol) in THF (300 mL) and hexane (80 mL) was slowly added a 2.5 M n-butyllithium hexane solution (19 mL) at -78°C. The reaction mixture was stirred at this temperature for 15 minutes and then carefully poured into 2N HCl solution (150 mL) to terminate the reaction. The organic and aqueous layers were separated and the aqueous layer was extracted with ether. All organic layers were combined, washed sequentially with NaHCO3 solution, water and brine, dried over anhydrous MgSO4 and concentrated. Purification by silica gel column chromatography (eluent: 10-20% ethyl acetate in hexane solution) afforded 6-(trifluoromethyl)-1-indanone (2.2 g, yield 51%) as an oil.MS (ESI) calculated value of C10H7F3O(M+H)+: 201.0; measured value: 201.0.
