4-(bromomethyl)-1-methoxy-2,3-dihydro-1H-indene

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a hot (110° C.) solution of 2.41 g (10.0 mmol) of 4-(bromomethyl)-1-methoxyindane in 40 ml of toluene 0.20 g of TsOH was added. This mixture was refluxed for 2 hours using a Dean-Stark head. The resulting mixture was passed through short column (4 cm) with silica gel 60 (40-63 μm), the silica gel layer was additionally washed by 20 ml of toluene. The combined elute was evaporated to dryness, the product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes). Yield 1.98 g (95%) of the title material. Anal. calc. for C10H9Br: C, 57.44; H, 4.34. Found: C, 57.32; H, 4.41. 1H NMR (CDCl3): δ 7.40 (m, 1H, 4-H), 7.29 (m, 1H, 5-H), 7.22 (m, 1H, 6-H), 6.92 (m, 1H, 3-H), 6.63 (m, 1H, 2-H), 4.62 (s, 2H, CH2Br), 3.48 (m, 2H, 1,1′-H). This mixture was refluxed for 2 hours the silica gel layer was additionally washed by 20 ml of toluene The combined elute was evaporated to dryness the product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes)

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

Procedure: To a hot (110° C.) solution of 2.41 g (10.0 mmol) of 4-(bromomethyl)-1-methoxyindane in 40 ml of toluene 0.20 g of TsOH was added. This mixture was refluxed for 2 hours using a Dean-Stark head. The resulting mixture was passed through short column (4 cm) with silica gel 60 (40-63 μm), the silica gel layer was additionally washed by 20 ml of toluene. The combined elute was evaporated to dryness, the product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes). Yield 1.98 g (95%) of the title material. Anal. calc. for C10H9Br: C, 57.44; H, 4.34. Found: C, 57.32; H, 4.41. 1H NMR (CDCl3): δ 7.40 (m, 1H, 4-H), 7.29 (m, 1H, 5-H), 7.22 (m, 1H, 6-H), 6.92 (m, 1H, 3-H), 6.63 (m, 1H, 2-H), 4.62 (s, 2H, CH2Br), 3.48 (m, 2H, 1,1′-H). This mixture was refluxed for 2 hours the silica gel layer was additionally washed by 20 ml of toluene The combined elute was evaporated to dryness the product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 90.0 g (0.40 mol) of 4-bromo-1-methoxyindane in 200 ml of anhydrous THF 166 ml (0.42 mol) 2.5 M solution of nBuLi in hexanes was added dropwise by vigorous stirring at −78° C. This solution was stirred at this temperature for 1 hour, cooled to −100° C., and then 57.9 g (0.80 mol) of DMF was added dropwise to maintain temperature of the reaction mixture below −70° C. Further on, this mixture was stirred at room temperature for 3 hours, and then 15 ml of water was added. The resulting mixture was evaporated to dryness. The residue dried in vacuum was dissolved in a mixture of 600 ml of THF and 300 ml of methanol. To this solution 48.2 g (1.27 mol) of NaBH4 was added in small portions by vigorous stirring at 0° C. This mixture was stirred for 12 hours at room temperature and then evaporated to dryness. The formed alcohol was extracted from a mixture of the residue with 800 ml of water by 2×400 ml of dichloromethane. The combined organic extract was dried over Na2SO4 and then evaporated to dryness. The residue was dissolved in 1 liter of THF, and 104 g (0.40 mol) of triphenylphosphine was added. This mixture was stirred for 10 minutes, and then 70.5 g (0.40 mol) of N-bromosuccinimide was added. The resulting mixture was stirred for 30 minutes at room temperature. The product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes and then hexanes-ether=10:1, vol.). Yield 74.7 g (78%) of the title material. Anal. calc. for C11H13BrO: C, 54.79; H, 5.43. Found: C, 54.55; H, 5.54. 1H NMR (CDCl3): δ 7.43 (m, 1H, 7-H), 7.31 (m, 1H, 5-H), 7.27 (m, 1H, 6H), 4.88 (dd, J=6.3 Hz, J=4.0 Hz, 1H, CHOMe), 4.52 (m, 2H, CH2Br), 3.47 (s, 3H, OMe), 3.15 (m, 1H, 3-H), 2.93 (m, 1H, 3′-H), 2.42 (m, 1H, 2-H), 2.19 (m, 1H, 2′-H). This solution was stirred at this temperature for 1 hour cooled to −100° C. to maintain temperature of the reaction mixture below −70° C Further on, this mixture was stirred at room temperature for 3 hours The resulting mixture was evaporated to dryness The residue dried in vacuum was dissolved in a mixture of 600 ml of THF and 300 ml of methanol by vigorous stirring at 0° C This mixture was stirred for 12 hours at room temperature evaporated to dryness The formed alcohol was extracted from a mixture of the residue with 800 ml of water by 2×400 ml of dichloromethane The combined organic extract was dried over Na2SO4 evaporated to dryness The residue was dissolved in 1 liter of THF This mixture was stirred for 10 minutes The resulting mixture was stirred for 30 minutes at room temperature The product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a hot (110° C.) solution of 2.41 g (10.0 mmol) of 4-(bromomethyl)-1-methoxyindane in 40 ml of toluene 0.20 g of TsOH was added. This mixture was refluxed for 2 hours using a Dean-Stark head. The resulting mixture was passed through short column (4 cm) with silica gel 60 (40-63 μm), the silica gel layer was additionally washed by 20 ml of toluene. The combined elute was evaporated to dryness, the product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes). Yield 1.98 g (95%) of the title material. Anal. calc. for C10H9Br: C, 57.44; H, 4.34. Found: C, 57.32; H, 4.41. 1H NMR (CDCl3): δ 7.40 (m, 1H, 4-H), 7.29 (m, 1H, 5-H), 7.22 (m, 1H, 6-H), 6.92 (m, 1H, 3-H), 6.63 (m, 1H, 2-H), 4.62 (s, 2H, CH2Br), 3.48 (m, 2H, 1,1′-H). This mixture was refluxed for 2 hours the silica gel layer was additionally washed by 20 ml of toluene The combined elute was evaporated to dryness the product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 90.0 g (0.40 mol) of 4-bromo-1-methoxyindane in 200 ml of anhydrous THF 166 ml (0.42 mol) 2.5 M solution of nBuLi in hexanes was added dropwise by vigorous stirring at −78° C. This solution was stirred at this temperature for 1 hour, cooled to −100° C., and then 57.9 g (0.80 mol) of DMF was added dropwise to maintain temperature of the reaction mixture below −70° C. Further on, this mixture was stirred at room temperature for 3 hours, and then 15 ml of water was added. The resulting mixture was evaporated to dryness. The residue dried in vacuum was dissolved in a mixture of 600 ml of THF and 300 ml of methanol. To this solution 48.2 g (1.27 mol) of NaBH4 was added in small portions by vigorous stirring at 0° C. This mixture was stirred for 12 hours at room temperature and then evaporated to dryness. The formed alcohol was extracted from a mixture of the residue with 800 ml of water by 2×400 ml of dichloromethane. The combined organic extract was dried over Na2SO4 and then evaporated to dryness. The residue was dissolved in 1 liter of THF, and 104 g (0.40 mol) of triphenylphosphine was added. This mixture was stirred for 10 minutes, and then 70.5 g (0.40 mol) of N-bromosuccinimide was added. The resulting mixture was stirred for 30 minutes at room temperature. The product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes and then hexanes-ether=10:1, vol.). Yield 74.7 g (78%) of the title material. Anal. calc. for C11H13BrO: C, 54.79; H, 5.43. Found: C, 54.55; H, 5.54. 1H NMR (CDCl3): δ 7.43 (m, 1H, 7-H), 7.31 (m, 1H, 5-H), 7.27 (m, 1H, 6H), 4.88 (dd, J=6.3 Hz, J=4.0 Hz, 1H, CHOMe), 4.52 (m, 2H, CH2Br), 3.47 (s, 3H, OMe), 3.15 (m, 1H, 3-H), 2.93 (m, 1H, 3′-H), 2.42 (m, 1H, 2-H), 2.19 (m, 1H, 2′-H). This solution was stirred at this temperature for 1 hour cooled to −100° C. to maintain temperature of the reaction mixture below −70° C Further on, this mixture was stirred at room temperature for 3 hours The resulting mixture was evaporated to dryness The residue dried in vacuum was dissolved in a mixture of 600 ml of THF and 300 ml of methanol by vigorous stirring at 0° C This mixture was stirred for 12 hours at room temperature evaporated to dryness The formed alcohol was extracted from a mixture of the residue with 800 ml of water by 2×400 ml of dichloromethane The combined organic extract was dried over Na2SO4 evaporated to dryness The residue was dissolved in 1 liter of THF This mixture was stirred for 10 minutes The resulting mixture was stirred for 30 minutes at room temperature The product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent