4-bromo-2-propan-2-yl-2,3-dihydroinden-1-one

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 73.4 g (0.29 mol) of 4-bromo-2-isopropylindan-1-one in 530 ml of a mixture of THF-methanol (2:1, vol.), 22.0 g (0.58 mol) of NaBH4 was added in small portions while vigorously stirring for 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 600 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic fractions were evaporated to dryness. The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg). Yield 57.8 g (84%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic fractions were evaporated to dryness The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 73.4 g (0.29 mol) of 4-bromo-2-isopropylindan-1-one in 530 ml of a mixture of THF-methanol (2:1, vol.), 22.0 g (0.58 mol) of NaBH4 was added in small portions while vigorously stirring for 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 600 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic fractions were evaporated to dryness. The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg). Yield 57.8 g (84%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic fractions were evaporated to dryness The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg)

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

Procedure: To a solution of 99.1 g (0.49 mol) of diethyl isopropylmalonate in 500 ml of THF, 11.7 g (0.49 mol) of sodium hydride was added. This mixture was refluxed for 1 h and then cooled to room temperature. Next, 120 g (0.49 mol) of 2-bromobenzylbromide was added, and the resulting mixture was refluxed for 3 h. This mixture was cooled to ambient temperature and filtered through a glass frit (G2). The precipitate (NaBr) was additionally washed with 3×100 ml of THF. The combined filtrate was evaporated to dryness. The residue was dissolved in 400 ml of ethanol and 160 g of potassium hydroxide and 50 ml of water were added. The resulting mixture was refluxed for 4 h, and then 200 ml of water was added. Ethanol was distilled off at atmospheric pressure. The resulting aqueous solution was acidified with 5 M HCl to pH 1. The precipitate obtained at −30° C. was filtered off, washed with 100 ml of water, and dried in air. The dibasic acid was decarboxylated by heating for 2 h at 160° C. The product obtained was dissolved in 600 ml of dichloromethane, and 600 ml of SOCl2 was added. The mixture was refluxed for 3 h and then evaporated to dryness. The residue was dissolved in 270 ml of dry dichloromethane, and the solution obtained was added dropwise to a suspension of 136 g (1.02 mol) of AlCl3 in 1350 ml of dichloromethane for 1 h at 0° C., while vigorously stirring. Next, the reaction mixture was refluxed for 3 h, cooled to ambient temperature, poured on 500 cm3 of ice, and, finally, acidified with 8M HCl to pH 3. The organic layer was separated, the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg). Yield 73.4 g (60%). This mixture was refluxed for 1 h the resulting mixture was refluxed for 3 h This mixture was cooled to ambient temperature filtered through a glass frit (G2) The precipitate (NaBr) was additionally washed with 3×100 ml of THF The combined filtrate was evaporated to dryness The residue was dissolved in 400 ml of ethanol 160 g of potassium hydroxide and 50 ml of water were added The resulting mixture was refluxed for 4 h 200 ml of water was added Ethanol was distilled off at atmospheric pressure The precipitate obtained at −30° C. was filtered off washed with 100 ml of water dried in air by heating for 2 h at 160° C The product obtained The mixture was refluxed for 3 h evaporated to dryness The residue was dissolved in 270 ml of dry dichloromethane the solution obtained Next, the reaction mixture was refluxed for 3 h cooled to ambient temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg)

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

Procedure: To a solution of 99.1 g (0.49 mol) of diethyl isopropylmalonate in 500 ml of THF, 11.7 g (0.49 mol) of sodium hydride was added. This mixture was refluxed for 1 h and then cooled to room temperature. Next, 120 g (0.49 mol) of 2-bromobenzylbromide was added, and the resulting mixture was refluxed for 3 h. This mixture was cooled to ambient temperature and filtered through a glass frit (G2). The precipitate (NaBr) was additionally washed with 3×100 ml of THF. The combined filtrate was evaporated to dryness. The residue was dissolved in 400 ml of ethanol and 160 g of potassium hydroxide and 50 ml of water were added. The resulting mixture was refluxed for 4 h, and then 200 ml of water was added. Ethanol was distilled off at atmospheric pressure. The resulting aqueous solution was acidified with 5 M HCl to pH 1. The precipitate obtained at −30° C. was filtered off, washed with 100 ml of water, and dried in air. The dibasic acid was decarboxylated by heating for 2 h at 160° C. The product obtained was dissolved in 600 ml of dichloromethane, and 600 ml of SOCl2 was added. The mixture was refluxed for 3 h and then evaporated to dryness. The residue was dissolved in 270 ml of dry dichloromethane, and the solution obtained was added dropwise to a suspension of 136 g (1.02 mol) of AlCl3 in 1350 ml of dichloromethane for 1 h at 0° C., while vigorously stirring. Next, the reaction mixture was refluxed for 3 h, cooled to ambient temperature, poured on 500 cm3 of ice, and, finally, acidified with 8M HCl to pH 3. The organic layer was separated, the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg). Yield 73.4 g (60%). This mixture was refluxed for 1 h the resulting mixture was refluxed for 3 h This mixture was cooled to ambient temperature filtered through a glass frit (G2) The precipitate (NaBr) was additionally washed with 3×100 ml of THF The combined filtrate was evaporated to dryness The residue was dissolved in 400 ml of ethanol 160 g of potassium hydroxide and 50 ml of water were added The resulting mixture was refluxed for 4 h 200 ml of water was added Ethanol was distilled off at atmospheric pressure The precipitate obtained at −30° C. was filtered off washed with 100 ml of water dried in air by heating for 2 h at 160° C The product obtained The mixture was refluxed for 3 h evaporated to dryness The residue was dissolved in 270 ml of dry dichloromethane the solution obtained Next, the reaction mixture was refluxed for 3 h cooled to ambient temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 73.4 g (0.29 mol) of 4-bromo-2-isopropylindan-1-one in 530 ml of a mixture of THF-methanol (2:1, vol.), 22.0 g (0.58 mol) of NaBH4 was added in small portions while vigorously stirring for 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 600 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic fractions were evaporated to dryness. The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg). Yield 57.8 g (84%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic fractions were evaporated to dryness The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg)

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

Procedure: To a solution of 99.1 g (0.49 mol) of diethyl isopropylmalonate in 500 ml of THF, 11.7 g (0.49 mol) of sodium hydride was added. This mixture was refluxed for 1 h and then cooled to room temperature. Next, 120 g (0.49 mol) of 2-bromobenzylbromide was added, and the resulting mixture was refluxed for 3 h. This mixture was cooled to ambient temperature and filtered through a glass frit (G2). The precipitate (NaBr) was additionally washed with 3×100 ml of THF. The combined filtrate was evaporated to dryness. The residue was dissolved in 400 ml of ethanol and 160 g of potassium hydroxide and 50 ml of water were added. The resulting mixture was refluxed for 4 h, and then 200 ml of water was added. Ethanol was distilled off at atmospheric pressure. The resulting aqueous solution was acidified with 5 M HCl to pH 1. The precipitate obtained at −30° C. was filtered off, washed with 100 ml of water, and dried in air. The dibasic acid was decarboxylated by heating for 2 h at 160° C. The product obtained was dissolved in 600 ml of dichloromethane, and 600 ml of SOCl2 was added. The mixture was refluxed for 3 h and then evaporated to dryness. The residue was dissolved in 270 ml of dry dichloromethane, and the solution obtained was added dropwise to a suspension of 136 g (1.02 mol) of AlCl3 in 1350 ml of dichloromethane for 1 h at 0° C., while vigorously stirring. Next, the reaction mixture was refluxed for 3 h, cooled to ambient temperature, poured on 500 cm3 of ice, and, finally, acidified with 8M HCl to pH 3. The organic layer was separated, the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg). Yield 73.4 g (60%). This mixture was refluxed for 1 h the resulting mixture was refluxed for 3 h This mixture was cooled to ambient temperature filtered through a glass frit (G2) The precipitate (NaBr) was additionally washed with 3×100 ml of THF The combined filtrate was evaporated to dryness The residue was dissolved in 400 ml of ethanol 160 g of potassium hydroxide and 50 ml of water were added The resulting mixture was refluxed for 4 h 200 ml of water was added Ethanol was distilled off at atmospheric pressure The precipitate obtained at −30° C. was filtered off washed with 100 ml of water dried in air by heating for 2 h at 160° C The product obtained The mixture was refluxed for 3 h evaporated to dryness The residue was dissolved in 270 ml of dry dichloromethane the solution obtained Next, the reaction mixture was refluxed for 3 h cooled to ambient temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 73.4 g (0.29 mol) of 4-bromo-2-isopropylindan-1-one in 530 ml of a mixture of THF-methanol (2:1, vol.), 22.0 g (0.58 mol) of NaBH4 was added in small portions while vigorously stirring for 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 600 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic fractions were evaporated to dryness. The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg). Yield 57.8 g (84%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic fractions were evaporated to dryness The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg)

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

Procedure: To a solution of 99.1 g (0.49 mol) of diethyl isopropylmalonate in 500 ml of THF, 11.7 g (0.49 mol) of sodium hydride was added. This mixture was refluxed for 1 h and then cooled to room temperature. Next, 120 g (0.49 mol) of 2-bromobenzylbromide was added, and the resulting mixture was refluxed for 3 h. This mixture was cooled to ambient temperature and filtered through a glass frit (G2). The precipitate (NaBr) was additionally washed with 3×100 ml of THF. The combined filtrate was evaporated to dryness. The residue was dissolved in 400 ml of ethanol and 160 g of potassium hydroxide and 50 ml of water were added. The resulting mixture was refluxed for 4 h, and then 200 ml of water was added. Ethanol was distilled off at atmospheric pressure. The resulting aqueous solution was acidified with 5 M HCl to pH 1. The precipitate obtained at −30° C. was filtered off, washed with 100 ml of water, and dried in air. The dibasic acid was decarboxylated by heating for 2 h at 160° C. The product obtained was dissolved in 600 ml of dichloromethane, and 600 ml of SOCl2 was added. The mixture was refluxed for 3 h and then evaporated to dryness. The residue was dissolved in 270 ml of dry dichloromethane, and the solution obtained was added dropwise to a suspension of 136 g (1.02 mol) of AlCl3 in 1350 ml of dichloromethane for 1 h at 0° C., while vigorously stirring. Next, the reaction mixture was refluxed for 3 h, cooled to ambient temperature, poured on 500 cm3 of ice, and, finally, acidified with 8M HCl to pH 3. The organic layer was separated, the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg). Yield 73.4 g (60%). This mixture was refluxed for 1 h the resulting mixture was refluxed for 3 h This mixture was cooled to ambient temperature filtered through a glass frit (G2) The precipitate (NaBr) was additionally washed with 3×100 ml of THF The combined filtrate was evaporated to dryness The residue was dissolved in 400 ml of ethanol 160 g of potassium hydroxide and 50 ml of water were added The resulting mixture was refluxed for 4 h 200 ml of water was added Ethanol was distilled off at atmospheric pressure The precipitate obtained at −30° C. was filtered off washed with 100 ml of water dried in air by heating for 2 h at 160° C The product obtained The mixture was refluxed for 3 h evaporated to dryness The residue was dissolved in 270 ml of dry dichloromethane the solution obtained Next, the reaction mixture was refluxed for 3 h cooled to ambient temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 73.4 g (0.29 mol) of 4-bromo-2-isopropylindan-1-one in 530 ml of a mixture of THF-methanol (2:1, vol.), 22.0 g (0.58 mol) of NaBH4 was added in small portions while vigorously stirring for 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 600 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic fractions were evaporated to dryness. The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg). Yield 57.8 g (84%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic fractions were evaporated to dryness The product was isolated by vacuum distillation (bp 128-132° C./4 mm Hg)

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

Procedure: To a solution of 99.1 g (0.49 mol) of diethyl isopropylmalonate in 500 ml of THF, 11.7 g (0.49 mol) of sodium hydride was added. This mixture was refluxed for 1 h and then cooled to room temperature. Next, 120 g (0.49 mol) of 2-bromobenzylbromide was added, and the resulting mixture was refluxed for 3 h. This mixture was cooled to ambient temperature and filtered through a glass frit (G2). The precipitate (NaBr) was additionally washed with 3×100 ml of THF. The combined filtrate was evaporated to dryness. The residue was dissolved in 400 ml of ethanol and 160 g of potassium hydroxide and 50 ml of water were added. The resulting mixture was refluxed for 4 h, and then 200 ml of water was added. Ethanol was distilled off at atmospheric pressure. The resulting aqueous solution was acidified with 5 M HCl to pH 1. The precipitate obtained at −30° C. was filtered off, washed with 100 ml of water, and dried in air. The dibasic acid was decarboxylated by heating for 2 h at 160° C. The product obtained was dissolved in 600 ml of dichloromethane, and 600 ml of SOCl2 was added. The mixture was refluxed for 3 h and then evaporated to dryness. The residue was dissolved in 270 ml of dry dichloromethane, and the solution obtained was added dropwise to a suspension of 136 g (1.02 mol) of AlCl3 in 1350 ml of dichloromethane for 1 h at 0° C., while vigorously stirring. Next, the reaction mixture was refluxed for 3 h, cooled to ambient temperature, poured on 500 cm3 of ice, and, finally, acidified with 8M HCl to pH 3. The organic layer was separated, the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg). Yield 73.4 g (60%). This mixture was refluxed for 1 h the resulting mixture was refluxed for 3 h This mixture was cooled to ambient temperature filtered through a glass frit (G2) The precipitate (NaBr) was additionally washed with 3×100 ml of THF The combined filtrate was evaporated to dryness The residue was dissolved in 400 ml of ethanol 160 g of potassium hydroxide and 50 ml of water were added The resulting mixture was refluxed for 4 h 200 ml of water was added Ethanol was distilled off at atmospheric pressure The precipitate obtained at −30° C. was filtered off washed with 100 ml of water dried in air by heating for 2 h at 160° C The product obtained The mixture was refluxed for 3 h evaporated to dryness The residue was dissolved in 270 ml of dry dichloromethane the solution obtained Next, the reaction mixture was refluxed for 3 h cooled to ambient temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The product was isolated by vacuum distillation (bp 154-157° C./3 mm Hg)