Reaction SMILES: FC(F)(F)C1C=CC(C2C=CC(CC(Cl)=O)=CC=2)=CC=1.COC(=O)COC1C=CC=C2C=1CCC2.C[O:37][C:38](=[O:68])[CH2:39][O:40][C:41]1[CH:49]=[CH:48][C:47]([CH2:50][CH2:51][C:52]2[CH:57]=[CH:56][C:55]([C:58]3[CH:63]=[CH:62][C:61]([C:64]([F:67])([F:66])[F:65])=[CH:60][CH:59]=3)=[CH:54][CH:53]=2)=[C:46]2[C:42]=1[CH2:43][CH2:44][CH2:45]2.C([SiH](CC)CC)C>ClCCCl.[Cl-].[Na+].O.FC(F)(F)C(O)=O.O>[F:65][C:64]([F:66])([F:67])[C:61]1[CH:60]=[CH:59][C:58]([C:55]2[CH:56]=[CH:57][C:52]([CH2:51][CH2:50][C:47]3[CH:48]=[CH:49][C:41]([O:40][CH2:39][C:38]([OH:68])=[O:37])=[C:42]4[C:46]=3[CH2:45][CH2:44][CH2:43]4)=[CH:53][CH:54]=2)=[CH:63][CH:62]=1
Reactant: COC(=O)COc1ccc(CCc2ccc(-c3ccc(C(F)(F)F)cc3)cc2)c2c1CCC2
Agent: CC[SiH](CC)CC
Agent: COC(=O)COc1cccc2c1CCC2
Agent: O=C(Cl)Cc1ccc(-c2ccc(C(F)(F)F)cc2)cc1
Solvent: O
Solvent: ClCCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)COc1ccc(CCc2ccc(-c3ccc(C(F)(F)F)cc3)cc2)c2c1CCC2
Temperature: 0 °C

Procedure:
Preparation of (Indan-4-yloxy)-acetic acid methyl ester (compound 91A) Compound 91A was prepared from indan-4-ol and bromo-acetic acid methyl ester in the manner analogous to Example 1C. 400 MHz 1H NMR (DMSO-d6) δ 7.00 (t, 1H, J=7.8 Hz), 6.79 (d, 1H, J=7.3 Hz), 6.56 (d, 1H, J=8.1 Hz), 4.74 (s, 2H), 3.63 (s, 3H), 2.77 (m, 4H), 1.95 (m, 2H). Step 2. Preparation of (4′-Trifluoromethyl-biphenyl-4-yl)-acetic acid (compound 91B) A mixture of (4-bromo-phenyl)-acetic acid (10.2 g, 47.4 mmol), 4-trifluoromethylphenylboronic acid (10.0 g, 52.7 mmol), and 50% water-wet 5% palladium on charcoal catalyst (4.6 g) in 50 ml of water and 8.0 ml of 2-propanol was treated dropwise over 30 minutes with a solution of sodium carbonate (6.8 g, 64.2 mmol) in 18 ml of water. The mixture was heated at 65-70° C. for 3 h, then cooled to 40° C. and treated with 13.0 ml of a solution of 2-propanol/water/2.0 N aqueous sodium hydroxide solution (70/15/1). The reaction mixture was filtered through a bed of Celite filter-aid, and the filter cake was washed 5× with the above 2-propanol/water/2.0 N aqueous sodium hydroxide solution. The combined filtrates were diluted with 125 ml of water, and the solution was digested on the steam bath with charcoal and filtered. The filtrate was diluted with an additional 150 ml of water and made strongly acidic by the addition of 4.0 N hydrochloric acid. The precipitated product was filtered and suspended in 350 ml of water plus 50 ml of methanol. The new mixture was stirred for several hours and filtered again. The crude product was recrystallized from aqueous acetonitrile. A sample recrystallized a second time from aqueous acetonitrile had mp 158-160° C.; MS m/z 280 (M). Step 3. Preparation of (4′-Trifluoromethyl-biphenyl-4-yl)-acetyl chloride (compound 91C) A suspension 91B (2.0 g, 7.1 mmol) and 5 drops of N,N-dimethylformamide in 30 ml of dichloromethane was cooled in ice and treated dropwise with a solution of oxalyl chloride (0.70 ml, 1.0 g, 8.0 mmol) in 10 ml of dichloromethane. The ice bath was removed, and the mixture was stirred at room temperature for 3 h. The solution was filtered, and the filtrate was evaporated. The residue quickly crystallized to yield the acid chloride intermediate, which was used immediately in the next step. Step 4. Preparation of {7-[2-(4′-Trifluoromethyl-biphenyl-4-yl-acetyl]-indan-4-yloxy}-acetic acid methyl ester (compound 91D) A solution of 91C (2.1 g, 7.0 mmol) in 25 ml of 1,2-dichloro-ethane was cooled in ice and treated with anhydrous ferric chloride (1.2 g, 7.4 mmol). The mixture was stirred, and a solution of 91A (1.5 g, 7.3 mmol) in 10 ml of 1,2-dichloro-ethane was added dropwise. The mixture was stirred at room temperature for 18 h. The reaction mixture was added to 300 g of ice and of brine and extracted with ethyl acetate (4×100 ml). The combined extracts were washed with 5% aqueous sodium bicarbonate solution (4×250 ml) and brine (1×250 ml), then dried over anhydrous sodium sulfate and concentrated. The crude product was purified by normal phase chromatography. A sample recrystallized from ethyl acetate/hexane had mp 141-143° C.; MS m/z 467 (M−1). Step 5. Preparation of {7-[2-(4′-Trifluoromethyl-biphenyl-4-yl)-ethyl]-indan-4-yloxy}-acetic acid methyl ester (compound 91E) A solution of 91D (1.0 g, 2.1 mmol) in 10.0 ml of trifluoroacetic acid was treated dropwise with triethylsilane (1.5 ml, 1.1 g, 9.4 mmol). The mixture was stirred at room temperature for 3 h and then added to 200 g of ice and water. The precipitated solid was extracted out with ethyl acetate (4×100 ml). The combined extracts were washed with brine (1×250 ml), 5% aqueous sodium bicarbonate solution (4×250 ml), and brine again, then dried over anhydrous sodium sulfate and concentrated. The crude product was purified by normal phase chromatography. 400 MHz 1H NMR (DMSO-d6) δ 7.82 (d, 2H, J=8.3 Hz), 7.75 (d, 2H, J=8.3 Hz), 7.61 (d, 2H, J=8.3 Hz), 7.30 (d, 2H, J=8.3 Hz), 6.90 (d, 1H, J=8.3 Hz), 6.53 (d, 1H, J=8.3 Hz), 4.71 (s, 2H), 3.63 (s, 2H), 2.77 (m, 8H), 1.94 (m, 2H). Step 6. Preparation of {7-[2-(4′-Trifluoromethyl-biphenyl-4-yl)-ethyl]-indan-4-yloxy}-acetic acid (compound 91) The title compound was prepared in the manner analogous to Example 1 using 91E. mp 188-190° C.; IR (thin film) cm−1: 1745, 1322, 1252, 1170, 1112, 1071; 400 MHz 1H NMR (DMSO-d6) δ 12.89 (br s, 1H), 7.83 (d, 2H, J=8.1 Hz), 7.74 (d, 2H, J=8.5 Hz), 7.61 (d, 2H, J=8.1 Hz), 7.30 (d, 2H, J=8.3 Hz), 6.90 (d, 1H, J=8.3 Hz), 6.51 (d, 1H, J=8.3 Hz), 4.58 (s, 2H), 2.75(m, 8H), 2.45 (m, 2H); MS m/z 439 (M−1). Anal. Calc'd for C26H23F3O3: C, 70.90; H, 5.26; found: C, 70.92; H, 5.01.