174702-59-1

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions with vigorous stirring over 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of MeI, and a solution of the crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of MeI was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4, and then evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil. This mixture was stirred at room temperature for 12 hours The hydrogenation product was extracted with 5×200 ml of dichloromethane the combined extract was evaporated to dryness This mixture was stirred for 2 hours at ambient temperature the mixture was additionally stirred for 2 hours The crude product was extracted with 5×200 ml of dichloromethane The combined extract was dried over Na2SO4 evaporated to dryness Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg Yield

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions with vigorous stirring over 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of MeI, and a solution of the crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of MeI was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4, and then evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil. This mixture was stirred at room temperature for 12 hours The hydrogenation product was extracted with 5×200 ml of dichloromethane the combined extract was evaporated to dryness This mixture was stirred for 2 hours at ambient temperature the mixture was additionally stirred for 2 hours The crude product was extracted with 5×200 ml of dichloromethane The combined extract was dried over Na2SO4 evaporated to dryness Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg Yield

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

Procedure: To a solution of 4.88 g of 2-methyl-4-bromo-1-indanone derived from 2-bromobenzyl bromide and diethyl methylmalonate in 12 ml of ethylene glycol was added 5.4 ml of ethyl orthoformate. After a catalytic amount of p-toluenesulfonic acid monohydrate was added, the mixture was stirred overnight at room temperature. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate and extracted with ether. After the organic layer was dried over magnesium sulfate, the solvent was removed by distillation under reduced pressure. The residual concentrate was purified by silica gel column chromatography to give 4.08 g of the title compound. extracted with ether After the organic layer was dried over magnesium sulfate the solvent was removed by distillation under reduced pressure The residual concentrate was purified by silica gel column chromatography

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions with vigorous stirring over 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of MeI, and a solution of the crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of MeI was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4, and then evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil. This mixture was stirred at room temperature for 12 hours The hydrogenation product was extracted with 5×200 ml of dichloromethane the combined extract was evaporated to dryness This mixture was stirred for 2 hours at ambient temperature the mixture was additionally stirred for 2 hours The crude product was extracted with 5×200 ml of dichloromethane The combined extract was dried over Na2SO4 evaporated to dryness Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg Yield

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions with vigorous stirring over 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of MeI, and a solution of the crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of MeI was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4, and then evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil. This mixture was stirred at room temperature for 12 hours The hydrogenation product was extracted with 5×200 ml of dichloromethane the combined extract was evaporated to dryness This mixture was stirred for 2 hours at ambient temperature the mixture was additionally stirred for 2 hours The crude product was extracted with 5×200 ml of dichloromethane The combined extract was dried over Na2SO4 evaporated to dryness Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg Yield

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

Procedure: To a solution of 4.88 g of 2-methyl-4-bromo-1-indanone derived from 2-bromobenzyl bromide and diethyl methylmalonate in 12 ml of ethylene glycol was added 5.4 ml of ethyl orthoformate. After a catalytic amount of p-toluenesulfonic acid monohydrate was added, the mixture was stirred overnight at room temperature. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate and extracted with ether. After the organic layer was dried over magnesium sulfate, the solvent was removed by distillation under reduced pressure. The residual concentrate was purified by silica gel column chromatography to give 4.08 g of the title compound. extracted with ether After the organic layer was dried over magnesium sulfate the solvent was removed by distillation under reduced pressure The residual concentrate was purified by silica gel column chromatography

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions with vigorous stirring over 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of Mel, and a solution of the crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of Mel was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4, and then evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil. This mixture was stirred at room temperature for 12 hours The hydrogenation product was extracted with 5×200 ml of dichloromethane the combined extract was evaporated to dryness This mixture was stirred for 2 hours at ambient temperature then, 92.0 g (40.4 ml, 0.664 mol) of Mel was added the mixture was additionally stirred for 2 hours The crude product was extracted with 5×200 ml of dichloromethane The combined extract was dried over Na2SO4 evaporated to dryness Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg Yield

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions with vigorous stirring over 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of Mel, and a solution of the crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of Mel was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4, and then evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil. This mixture was stirred at room temperature for 12 hours The hydrogenation product was extracted with 5×200 ml of dichloromethane the combined extract was evaporated to dryness This mixture was stirred for 2 hours at ambient temperature then, 92.0 g (40.4 ml, 0.664 mol) of Mel was added the mixture was additionally stirred for 2 hours The crude product was extracted with 5×200 ml of dichloromethane The combined extract was dried over Na2SO4 evaporated to dryness Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg Yield

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

Procedure: Under an argon atmosphere, following the procedure described for bis(2-methyl-1H-inden-7-yl)sulfide, 22.9 g (85.2 mmol) of the above-described dioxalane-protected 4-bromo-2-methylindanone in 150 ml of THF, 34.1 ml of 2.5 M (85.3 mmol) nBuLi in hexanes, and 4.39 g (42.6 mmol) of SCl2 in 35 ml of hexanes gave crude dioxalane-protected 2-methyl-4-[(2-methyl-1-oxo-2,3-dihydro-1H-inden-4-yl)sulfanyl]-1-indanone, which was deprotected in a mixture of 150 ml of 16 M HCl and 150 ml of methanol for 7 hours at reflux. The product was isolated by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 400 mm, eluant: CH2Cl2) and then recrystallized from hexanes. Yield, 3.53 g (26%) of a white solid. gave crude dioxalane-protected 2-methyl-4-[(2-methyl-1-oxo-2,3-dihydro-1H-inden-4-yl)sulfanyl]-1-indanone, which at reflux The product was isolated by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 400 mm, eluant: CH2Cl2) recrystallized from hexanes Yield

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

Procedure: Under an argon atmosphere, following the procedure described for bis(2-methyl-1H-inden-7-yl)sulfide, 22.9 g (85.2 mmol) of the above-described dioxalane-protected 4-bromo-2-methylindanone in 150 ml of THF, 34.1 ml of 2.5 M (85.3 mmol) nBuLi in hexanes, and 4.39 g (42.6 mmol) of SCl2 in 35 ml of hexanes gave crude dioxalane-protected 2-methyl-4-[(2-methyl-1-oxo-2,3-dihydro-1H-inden-4-yl)sulfanyl]-1-indanone, which was deprotected in a mixture of 150 ml of 16 M HCl and 150 ml of methanol for 7 hours at reflux. The product was isolated by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 400 mm, eluant: CH2Cl2) and then recrystallized from hexanes. Yield, 3.53 g (26%) of a white solid. gave crude dioxalane-protected 2-methyl-4-[(2-methyl-1-oxo-2,3-dihydro-1H-inden-4-yl)sulfanyl]-1-indanone, which at reflux The product was isolated by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 400 mm, eluant: CH2Cl2) recrystallized from hexanes Yield

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

Procedure: Under an argon atmosphere, following the procedure described for bis(2-methyl-1H-inden-7-yl)sulfide, 22.9 g (85.2 mmol) of the above-described dioxalane-protected 4-bromo-2-methylindanone in 150 ml of THF, 34.1 ml of 2.5 M (85.3 mmol) nBuLi in hexanes, and 4.39 g (42.6 mmol) of SCl2 in 35 ml of hexanes gave crude dioxalane-protected 2-methyl-4-[(2-methyl-1-oxo-2,3-dihydro-1H-inden-4-yl)sulfanyl]-1-indanone, which was deprotected in a mixture of 150 ml of 16 M HCl and 150 ml of methanol for 7 hours at reflux. The product was isolated by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 400 mm, eluant: CH2Cl2) and then recrystallized from hexanes. Yield, 3.53 g (26%) of a white solid. gave crude dioxalane-protected 2-methyl-4-[(2-methyl-1-oxo-2,3-dihydro-1H-inden-4-yl)sulfanyl]-1-indanone, which at reflux The product was isolated by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 400 mm, eluant: CH2Cl2) recrystallized from hexanes Yield

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions at vigorous stirring for 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of MeI, and a solution of crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of MeI was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4 and, then, evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil. This mixture was stirred at room temperature for 12 hours The hydrogenation product was extracted with 5×200 ml of dichloromethane the combined extract was evaporated to dryness This mixture was stirred for 2 hours at ambient temperature the mixture was additionally stirred for 2 hours The crude product was extracted with 5×200 ml of dichloromethane The combined extract was dried over Na2SO4 evaporated to dryness Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg Yield