methyl 2-(5-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of pyridine (820 μL, 10.1 mmol) in dichloromethane (10 mL) cooled to 0° C. trifluoromethanesulfonic anhydride (1.56 mL, 9.28 mmol) was added. The resulting mixture was stirred for 5 min, and methyl (R/S)-(5-hydroxy-indan-1-yl)acetate (1.74 g, 8.44 mmol, from Step C) was added. The reaction mixture was warmed to ambient temperature, stirred for 1 hr and diluted with dichloromethane. The organic layer was washed with H2O, brine and dried over MgSO4. The mixture was filtered and concentrated in vacuo. Purification by flash chromatography (10% EtOAc/hexanes) on SiO2 gave 2.63 g of the title compound as a pale yellow liquid: 1H NMR (CDCl3) δ 1.83-1.88 (m, 1H), 2.47-2.55 (m, 2H), 2.78 (dd, 1H, J=6.0, 15.8 Hz), 2.92-3.01 (m, 2H), 3.62-3.65 (m, 1H), 3.76 (s, 3H), 7.09 (dd, 1H, J=2.3, 8.3 Hz), 7.16 (s, 1H), 7.25 (d, 1H, J=8.2 Hz). was added stirred for 1 hr The organic layer was washed with H2O, brine dried over MgSO4 The mixture was filtered concentrated in vacuo Purification by flash chromatography (10% EtOAc/hexanes) on SiO2

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.0 M solution of boron tribromide in dichloromethane (22.7 mL, 22.7 mmol) was added to an ice-cold solution of methyl (R/S)-(5-methoxy-indan-1-yl)acetate (2.00 g, 9.08 mmol, from Step B) in dichloromethane (15 mL). The cooling bath was removed and the reaction mixture stirred at ambient temperature. After 1 hr, the reaction mixture was slowly transferred to an ice-cold solution of methanol (50 mL). Methanol was removed in vacuo, and the residue was partitioned between EtOAc and sat. NaH2PO4. The organic layer was washed with H2O, brine, and dried over MgSO4. The mixture was filtered, concentrated in vacuo and purified by flash chromatography (15, 20% EtOAc/hexanes) on SiO2 to afford 1.74 g of the title compound: 1H NMR (CDCl3) δ 1.72-1.79 (m, 1H), 2.35-2.42 (m, 1H), 2.46 (dd, 1H, J=8.5, 15.3 Hz), 2.76 (dd, 1H, J=5.9, 15.3 Hz), 2.80-2.92 (m, 2H), 3.50-3.55 (m, 1H), 3.75 (s, 3H), 5.63-5.86 (brs, 1H), 6.67 (dd, 1H, J=2.4, 8.1 Hz), 6.74 (d, 1H, J=2.0 Hz), 7.01 (d, 1H, J=8.3 Hz). The cooling bath was removed Methanol was removed in vacuo the residue was partitioned between EtOAc and sat. NaH2PO4 The organic layer was washed with H2O, brine dried over MgSO4 The mixture was filtered concentrated in vacuo purified by flash chromatography (15, 20% EtOAc/hexanes) on SiO2