methyl 2,3-dihydro-1H-indene-1-carboxylate

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

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

Procedure: Indan-1-carboxylic acid methyl ester (17.6 g, 100 mmol) in 100 mL of THF was slowly added to a −60° C. solution of lithium diisopropylamide (from 15.4 mL (110 mmol) of diisopropylamine and 42 mL of 2.5M n-BuLi in hexane) in 200 mL of THF. After 15 min, methyl 5-bromopentanoate (20.5 g, 105 mmol) was added and the mixture was allowed to warm to room temperature and stirred for 12 h. Ether and water were added and the ether layer was separated, washed with water and brine, dried and evaporated. Purification by flash chromatography (10% ethyl acetate/hexane) afforded 15 g of 1-(4-ethoxycarbonyl-butyl)-indan-1-carboxylic acid methyl ester as an oil. the ether layer was separated washed with water and brine dried evaporated Purification by flash chromatography (10% ethyl acetate/hexane)

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

Procedure: To a −78° C. tetrahydrofuran solution containing methyl indane-1-carboxylate (2.10 g, 11.9 mmol) from Step A, was added a 1M tetrahydrofuran solution of NaHMDS (23.8 mL, 23.8 mmol). The mixture was stirred at −78° C. for 30 minutes. Benzyl bromide (1.49 mL, 12.5 mmol) was added and the reaction was warmed to 0° C. and stirred for 90 minutes. The reaction was quenched with aqueous sodium bicarbonate and then extracted into EtOAc (3×50 mL) and the combined organic washings were dried over MgSO4 and evaporated. The resulting residue was purified by column chromatography (98/2 hexanes/EtOAc) to afford of methyl 1-benzylindane-1-carboxylate (2.5 g, 79%) as a partially pure oil that was taken to the next step. the reaction was warmed to 0° C. stirred for 90 minutes The reaction was quenched with aqueous sodium bicarbonate extracted into EtOAc (3×50 mL) the combined organic washings were dried over MgSO4 evaporated The resulting residue was purified by column chromatography (98/2 hexanes/EtOAc)

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

Procedure: To a −78° C. tetrahydrofuran solution containing methyl indane-1-carboxylate (2.10 g, 11.9 mmol) from Step A, was added a 1M tetrahydrofuran solution of NaHMDS (23.8 mL, 23.8 mmol). The mixture was stirred at −78° C. for 30 minutes. Benzyl bromide (1.49 mL, 12.5 mmol) was added and the reaction was warmed to 0° C. and stirred for 90 minutes. The reaction was quenched with aqueous sodium bicarbonate and then extracted into EtOAc (3×50 mL) and the combined organic washings were dried over MgSO4 and evaporated. The resulting residue was purified by column chromatography (98/2 hexanes/EtOAc) to afford of methyl 1-benzylindane-1-carboxylate (2.5 g, 79%) as a partially pure oil that was taken to the next step. the reaction was warmed to 0° C. stirred for 90 minutes The reaction was quenched with aqueous sodium bicarbonate extracted into EtOAc (3×50 mL) the combined organic washings were dried over MgSO4 evaporated The resulting residue was purified by column chromatography (98/2 hexanes/EtOAc)

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

Procedure: Thionyl Chloride (0.95 mL, 13.0 mmol) was added to a room temperature solution of indane-1-carboxylic acid dissolved in 20 mL of dichloromethane. The reaction mixture was stirred at room temperature for 35 minutes after which time the volume was reduced by approximately 50% via a rotovap. Then 20 mL of methanol was added and the reaction was stirred at room temperature for 3 hours. Evaporation of the solvent and column chromatography (9/1 hexanes/EtOAc) afforded of methyl indane-1-carboxylate (2.2 g, 100%) as a colorless oil. the reaction was stirred at room temperature for 3 hours Evaporation of the solvent and column chromatography (9/1 hexanes/EtOAc)

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

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

Procedure: 18 g of finely powdered aluminium chloride are added in portions to a solution of 8 g of indane-1-carboxylic acid methyl ester and 8.2 g of benzoyl chloride in 100 ml of carbon disulphide, whilst stirring in an anhydrous atmosphere. After completion of the addition, the reaction mixture is heated for 2 hours to the reflux temperature. It is then allowed to cool to room temperature, poured onto a mixture of 100 g of ice and 50 ml of concentrated hydrochloric acid and extracted with twice 100 ml of ether. The organic phases are combined, washed with twice 100 ml of water, dried over sodium sulphate and evaporated in vacuo. Distillation of the evaporation residue in a high vacuum gives 6-benzoyl-indane-1-carboxylic acid methyl ester in the fraction boiling at 165°-170° C. (0.5 mm). After completion of the addition the reaction mixture is heated for 2 hours to the reflux temperature extracted with twice 100 ml of ether washed with twice 100 ml of water dried over sodium sulphate evaporated in vacuo Distillation of the evaporation residue in a high vacuum

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

Procedure: 18 g of finely powdered aluminum chloride are added in portions of a solution of 8 g of indane-1-carboxylic acid methyl ester and 8.2 g of benzoyl chloride in 100 ml of carbon disulphide, whilst stirring in an anhydrous atmosphere. After completion of the addition, the reaction mixture is heated for 2 hours to the reflux temperature. It is then allowed to cool to room temperature, poured onto a mixture of 100 g of ice and 50 ml of concentrated hydrochloric acid and extracted with twice 100 ml of ether. The organic phases are combined, washed with twice 100 ml of water, dried over sodium sulphate and evaporated in vacuo. Distillation of the evaporation residue in a high vacuum gives 6-benzoyl-indane-1-carboxylic acid methyl ester in the fraction boiling at 165°-170° C (0.5 mm). After completion of the addition the reaction mixture is heated for 2 hours to the reflux temperature extracted with twice 100 ml of ether washed with twice 100 ml of water dried over sodium sulphate evaporated in vacuo Distillation of the evaporation residue in a high vacuum

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

Procedure: Indan-1-carboxylic acid methyl ester (17.6 g, 100 mmol) in 100 mL of THF was slowly added to a −60° C. solution of lithium diisopropylamide (from 15.4 mL (110 mmol) of diisopropylamine and 42 mL of 2.5M n-BuLi in hexane) in 200 mL of THF. After 15 min, methyl 5-bromopentanoate (20.5 g, 105 mmol) was added and the mixture was allowed to warm to room temperature and stirred for 12 h. Ether and water were added and the ether layer was separated, washed with water and brine, dried and evaporated. Purification by flash chromatography (10% ethyl acetate/hexane) afforded 15 g of 1-(4-ethoxycarbonyl-butyl)-indan-1-carboxylic acid methyl ester as an oil. the ether layer was separated washed with water and brine dried evaporated Purification by flash chromatography (10% ethyl acetate/hexane)

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

Procedure: To a −78° C. tetrahydrofuran solution containing methyl indane-1-carboxylate (2.10 g, 11.9 mmol) from Step A, was added a 1M tetrahydrofuran solution of NaHMDS (23.8 mL, 23.8 mmol). The mixture was stirred at −78° C. for 30 minutes. Benzyl bromide (1.49 mL, 12.5 mmol) was added and the reaction was warmed to 0° C. and stirred for 90 minutes. The reaction was quenched with aqueous sodium bicarbonate and then extracted into EtOAc (3×50 mL) and the combined organic washings were dried over MgSO4 and evaporated. The resulting residue was purified by column chromatography (98/2 hexanes/EtOAc) to afford of methyl 1-benzylindane-1-carboxylate (2.5 g, 79%) as a partially pure oil that was taken to the next step. the reaction was warmed to 0° C. stirred for 90 minutes The reaction was quenched with aqueous sodium bicarbonate extracted into EtOAc (3×50 mL) the combined organic washings were dried over MgSO4 evaporated The resulting residue was purified by column chromatography (98/2 hexanes/EtOAc)

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

Procedure: Thionyl Chloride (0.95 mL, 13.0 mmol) was added to a room temperature solution of indane-1-carboxylic acid dissolved in 20 mL of dichloromethane. The reaction mixture was stirred at room temperature for 35 minutes after which time the volume was reduced by approximately 50% via a rotovap. Then 20 mL of methanol was added and the reaction was stirred at room temperature for 3 hours. Evaporation of the solvent and column chromatography (9/1 hexanes/EtOAc) afforded of methyl indane-1-carboxylate (2.2 g, 100%) as a colorless oil. the reaction was stirred at room temperature for 3 hours Evaporation of the solvent and column chromatography (9/1 hexanes/EtOAc)