5,6-dichloro-2,3-dihydroinden-1-one

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

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

Procedure: A solution of 12.3 g of 5,6-dichloro-1-indanone, 12.6 ml of 3-buten-2-ol and 125 mg of p-toluenesulfonic acid in 125 ml of 2,2-dimethoxy-propane was boiled under reflux for 68 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). In addition to 4.3 g of educt, there were obtained 10.8 g (69%) of (RS)-2-(2-buten-1-yl)-5,6-dichloro-1-indanone as a yellow oil. separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped) The reaction mixture was subsequently concentrated in a vacuum purified by column chromatography on silica gel (hexane/diethyl ether 4:1) In addition to 4.3 g of educt

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

Procedure: A solution of 12.3 g of 5,6-dichloro-1-indanone, 12.6 ml of 3-buten-2-ol and 125 mg of p-toluenesulfonic acid in 125 ml of 2,2-dimethoxy-propane was boiled under reflux for 68 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). In addition to 4.3 g of educt, there were obtained 10.8 g (69%) of (RS)-2-(2-buten-1-yl)-5,6-dichloro-1-indanone as a yellow oil. separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped) The reaction mixture was subsequently concentrated in a vacuum purified by column chromatography on silica gel (hexane/diethyl ether 4:1) In addition to 4.3 g of educt

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

Procedure: Following the procedure of Example 1, 5,6-dichloro-1-indanone was reacted with ammonium acetate and sodium cyanoborohydride to yield 5,6-dichloro-1-aminoindane; yield = 670 mg. The crystalline compound was treated with 360 mg. of maleic acid in 25 ml. of isopropanol. The maleate salt crystallized and was separated by filtration. Recrystallization of the salt from a 1:3 isopropanol/ethyl acetate solvent mixture yielded 650 mg. of 5,6-dichloro-1-aminoindane maleate melting at 167°-170° C.

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

Procedure: Following the procedure of Example 1, 5,6-dichloro-1-indanone was reacted with ammonium acetate and sodium cyanoborohydride to yield 5,6-dichloro-1-aminoindane; yield = 670 mg. The crystalline compound was treated with 360 mg. of maleic acid in 25 ml. of isopropanol. The maleate salt crystallized and was separated by filtration. Recrystallization of the salt from a 1:3 isopropanol/ethyl acetate solvent mixture yielded 650 mg. of 5,6-dichloro-1-aminoindane maleate melting at 167°-170° C.

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

Procedure: A solution of 12.3 g of 5,6-dichloro-1-indanone, 12.6 ml of 3-buten-2-ol and 125 mg of p-toluenesulfonic acid in 125 ml of 2,2-dimethoxy-propane was boiled under reflux for 68 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). In addition to 4.3 g of educt, there were obtained 10.8 g (69%) of (RS)-2-(2-buten-1-yl)-5,6-dichloro-1-indanone as a yellow oil. separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped) The reaction mixture was subsequently concentrated in a vacuum purified by column chromatography on silica gel (hexane/diethyl ether 4:1) In addition to 4.3 g of educt

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

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

Procedure: 4.85 g of sodium borohydride were added at 0° C. to a solution of 4 g of the product of Step A in 285 ml of methanol and after stirring for one hour, the methanol was evaporated. The residue was diluted with water and excess hydride was eliminated by addition of hydrochloric acid. The mixture was extracted with ethyl acetate and the organic phase was evaporated to dryness under reduced pressure to obtain the desired product melting at 84° C. the methanol was evaporated The residue was diluted with water and excess hydride was eliminated by addition of hydrochloric acid The mixture was extracted with ethyl acetate the organic phase was evaporated to dryness under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 20 g of 3-(3,4-dichlorophenyl)-propionic acid [J. Med. Chem., Vol. 16(2) (1973), p. 101-106 ] and 100 ml of thionyl chloride was refluxed for 30 minutes and the thionyl chloride was then evaporated. The residue was taken up in 20 ml of methylene chloride and the solution was poured into a suspension of 20 g of aluminum chloride in 150 ml of methylene chloride. The mixture was stirred for one hour at room temperature and 30 minutes at 50° C. The mixture was poured over ice and was stirred for 30 minutes and then was extracted with methylene chloride. The organic phase was washed with water, dried and evaporated to dryness and the residue was taken up in ether and vacuum filtered. The product was dried to obtain 80 g of the desired product melting at 155° C. was refluxed for 30 minutes the thionyl chloride was then evaporated the solution was poured into a suspension of 20 g of aluminum chloride in 150 ml of methylene chloride The mixture was poured over ice was stirred for 30 minutes was extracted with methylene chloride The organic phase was washed with water dried evaporated to dryness vacuum filtered The product was dried

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

Procedure: 4.85 g of sodium borohydride were added at 0° C. to a solution of 4 g of the product of Step A in 285 ml of methanol and after stirring for one hour, the methanol was evaporated. The residue was diluted with water and excess hydride was eliminated by addition of hydrochloric acid. The mixture was extracted with ethyl acetate and the organic phase was evaporated to dryness under reduced pressure to obtain the desired product melting at 84° C. the methanol was evaporated The residue was diluted with water and excess hydride was eliminated by addition of hydrochloric acid The mixture was extracted with ethyl acetate the organic phase was evaporated to dryness under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 20 g of 3-(3,4-dichlorophenyl)-propionic acid [J. Med. Chem., Vol. 16(2) (1973), p. 101-106] and 100 ml of thionyl chloride was refluxed for 30 minutes and the thionyl chloride was then evaporated. The residue was taken up in 20 ml of methylene chloride and the solution was poured into a suspension of 20 g of aluminum chloride in 150 ml of methylene chloride. The mixture was stirred for one hour at room temperature and 30 minutes at 50° C. The mixture was poured over ice and was stirred for 30 minutes and then was extracted with methylene chloride. was refluxed for 30 minutes the thionyl chloride was then evaporated the solution was poured into a suspension of 20 g of aluminum chloride in 150 ml of methylene chloride The mixture was poured over ice was stirred for 30 minutes was extracted with methylene chloride

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

Procedure: The 2-bromo-5,6-dichloro-1-indanone is prepared as in Example 14 for the preparation of 2-bromo-4-fluoro-1-indanone but starting with 5.48 g of 5,6-dichloro-1-indanone, 16.1 g of copper bromide and 175 ml of dioxane. After purifying by silica column chromatography with an ethyl acetate-cyclohexane mixture (10-90 by volume) as eluent, 4.07 g of 2-bromo-5,6-dichloro-1-indanone are obtained which melt at 85° C. After purifying by silica column chromatography with an ethyl acetate-cyclohexane mixture (10-90 by volume) as eluent