AlCl3-(4-Fluoro-phenyl)-propionic acid (5 g, 29.7 mmol; Compound E in FIG. 7) was added to polyphosphoric acid (PPA; 65.4 g, 0.654 mol) at 50° C. The viscous mixture was heated at 90° C. for 2 hours. The syrup was poured into ice water and stirred for 30 minutes. The aqueous mixture was extracted with ether (3.x.50 mL) and the combined organics were washed with HExample 150: (+/-)-3-[5-Chloro-2-(6-fluoro-indan-1 -yloxy)-phenoxy1-azetidine.; Step A: Preparation of (+/-)-6-fluoro-indan-1-ol.; To a solution of 6-fluoro- indan-1 -one (0.50 g, 3.3 mmol) in DCE (10 ml_) and MeOH (10 ml_) was added NaBH4 (0.25 g, 6.6 mmol). After 30 min the reaction was quenched with H2O (10 ml_) and extracted with CH2CI2 (3 x 20 ml_). The organic layers were combined and dried to give the title compound (0.49 g, 97%). MS (ESI): mass calcd. for C9H7FO, 150.1 ; m/z found, 151.4 [M+H]+. 1H NMR (CDCI3): 7.23 - 7.13 (m, 1 H), 7.09 (dd, J = 8.6, 2.5 Hz, 1 H), 6.99 - 6.90 (m, 1 H), 5.21 (t, J = 6.3 Hz, 1 H), 3.13 - 2.91 (m, 1 H), 2.85 - 2.68 (m, 1 H), 2.63 - 2.44 (m, 1 H), 2.09 - 1.74 (m, 2H).General procedure: NaBH4 (1.49 g, 39.3 mmol) was added to a solution of 6-methoxyindan-1-one (5.50 g, 33.9 mmol) in MeOH (100 mL) and stirred for 90 min at r.t. The reaction was quenched with H2O (400 mL) and themixture stirred for 15 min. The resulting mixture was extracted with Et2O (3 × 150 mL). The combined extracts were dried (MgSO4), filteredand concentrated to afford 6-methoxyindan-1-ol (5.82 g, quantitative yield) as a yellow oil.To a solution of A solution of the indanone (Compound F in FIG. 7; 2.06 g, 13.7 mmol) and ethyl bromoacetate (EBA; 3.44 g, 20.6 mmol) in benzene (10 mL) was added over a 5 minute period to activated zinc (3.77 g, 57.7 mmol) in benzene (21 mL) and ether (10 mL). A few crystals of iodine were added to initiate the reaction and the mixture was held at reflux. At 3 hour intervals, 2 batches of zinc (1.8 g, 27.5 mmol) and ethyl bromoacetate (EBA; 1.8 g, 10.8 mmol) were added and the mixture was refluxed overnight. The solution was cooled to room temperature and ethanol (5 mL) and acetic acid (23 mL) were added. The solution was poured into 1:1 aqueous acetic acid (100 mL) and the organic layer was separated. The aqueous phase was extracted with diethyl ether (Et2O; 2×25 mL) and the combined organics were washed with water, NaHCO3, water, dried (MgSO4), filtered, and concentrated in vacuo to give the crude product (Compound G in FIG. 7; 3.55 g).General procedure: To a solution of LDA or LHMDS (48.0 mmol, 2.0 equiv) in anhydrous THF (100 mL) was added EtOAc (61.0 mmol, 2.5 equiv) at -78 C. The mixture was stirred at -78 C for 30 min. To the resulting mixture was added dropwise a solution of indenone (24.0 mmol, 1.0 equiv) in anhydrous THF (20 mL). The mixture was stirred at -78 C for another 4 h and then quenched with a saturated aqueous NH4Cl. The mixture was extracted with EtOAc (20 mL × 3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. To the residue was added HOAc/ H2SO4 (10/1, 40 mL). After stirring for 4 h at room temperature, the mixture was extracted with EtOAc (15 mL × 3). The combined extracts were washed successively with water, saturated NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to afford inden-3-yl acetate.3-(4-Fluoro-phenyl)-propionic acid (5 g, 29.7 mmol; Compound E in FIG. 7) was added to polyphosphoric acid (PPA; 65.4 g, 0.654 mol) at 50 C. The viscous mixture was heated at 90 C. for 2 hours. The syrup was poured into ice water and stirred for 30 minutes. The aqueous mixture was extracted with ether (3×50 mL) and the combined organics were washed with H2O (2×50 mL) and NaHCO3 until neutralized. The resulting organic phase was washed with H2O (50 mL), dried (MgSO4), filtered, and concentrated in vacuo. Purification using flash chromatography (7:1 hexane/ethyl acetate (EtOAc)) afforded the indanone (Compound F in FIG. 7) as a yellow solid (2.06 g, 46%). 1H NMR (CDCl3) delta 7.45 (ddd, J=0.5, 4.5, 8.4 Hz, 1H), 7.39 (ddd, J=0.3, 2.6, 7.8 Hz, 1H), 7.30 (td, J=2.6, 8.6 Hz, 1H), 3.12 (t, J=5.7 Hz, 2H), 2.75 (m, 2H); ESI-CID 151 (M-H+).A mixture of 3-(4-fluorophenyl)propionic acid (20.0 g) and polyphosphoric acid (800 g) was stirred and heated at 100 C. for 2 hr. The mixture was then poured into an ice/water mixture (1 kg) and extracted with ethyl acetate. The organic phase was washed with water, dilute sodium bicarbonate solution and water again, then dried (MgSO4) and evaporated to give
skype
3YRS 
Chat On Messeger
