1-chloro-1,2,3,4-tetrahydronaphthalene

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

Procedure: Using 8-[3-(4-piperidinyl)propanoyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (500 mg) and (±)-1-chloro-1,2,3,4-tetrahydronaphthalene (280 mg) according to the same method as that of Example 330, the title compound (43 mg) was obtained as pale yellow amorphous powders.

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

Procedure: Using 8-[3-(4-piperidinyl)propanoyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (500 mg) and (±)-1-chloro-1,2,3,4-tetrahydronaphthalene (280 mg) according to the same method as that of Example 330, the title compound (43 mg) was obtained as pale yellow amorphous powders.

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

Procedure: One hundred grams of 1,2,3,4-tetrahydro-1-naphthol were dissolved in 1 liter of chloroform and 53.9 ml of pyridine. The mixture was cooled with an external ice bath and 98.6 ml of thionyl chloride were added over a 1 hour period. The reaction mixture was stirred an additional 2 hours with cooling, concentrated in vacuo, and the residue taken up in 1 liter of methylene chloride. The methylene chloride solution was washed with water, a 5% sodium bicarbonate solution, water again, dried over sodium sulfate, and evaporated to dryness to provide the desired intermediate 1,2,3,4-tetrahydro-1-chloronaphthalene. The mixture was cooled with an external ice bath with cooling concentrated in vacuo The methylene chloride solution was washed with water a 5% sodium bicarbonate solution, water again, dried over sodium sulfate evaporated to dryness

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

Procedure: One hundred grams of 1,2,3,4-tetrahydro-1-naphthol were dissolved in 1 liter of chloroform and 53.9 ml of pyridine. The mixture was cooled with an external ice bath and 98.6 ml of thionyl chloride were added over a 1 hour period. The reaction mixture was stirred an additional 2 hours with cooling, concentrated in vacuo, and the residue taken up in 1 liter of methylene chloride. The methylene chloride solution was washed with water, a 5% sodium bicarbonate solution, water again, dried over sodium sulfate, and evaporated to dryness to provide the desired intermediate 1,2,3,4-tetrahydro-1-chloronaphthalene. The mixture was cooled with an external ice bath with cooling concentrated in vacuo The methylene chloride solution was washed with water a 5% sodium bicarbonate solution, water again, dried over sodium sulfate evaporated to dryness

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

Procedure: Using 8-[3-(4-piperidinyl)propanoyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (500 mg) and (±)-1-chloro-1,2,3,4-tetrahydronaphthalene (280 mg) according to the same method as that of Example 330, the title compound (43 mg) was obtained as pale yellow amorphous powders.

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

Procedure: Using 8-[3-(4-piperidinyl)propanoyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (500 mg) and (±)-1-chloro-1,2,3,4-tetrahydronaphthalene (280 mg) according to the same method as that of Example 330, the title compound (43 mg) was obtained as pale yellow amorphous powders.

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

Procedure: Cyclopropanecarbonitrile (17.14 g) was added dropwise to a mixture of lithium diisopropylamide solution (2M in a mixture of heptane, tetrahydrofuran and ethylbenzene; 128 ml), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (30 ml) and tetrahydrofuran (240 ml) stirring at -78° C. under nitrogen. Stirring was continued for 1 hour at this temperature then a solution of 1-chlorotetralin (48.4 g) in tetrahydrofuran (50 ml) was added slowly and after a further hour the solution was allowed to warm to ambient temperature, then was heated under gentle reflux for 2 hours. The solvent was removed in vacuo and the residue acidified with concentrated hydrochloric acid then extracted with ethyl acetate (4×100 ml). The combined extracts were dried over magnesium sulphate and the solvent removed in vacuo to leave a semi-solid which was filtered and washed with acetonitrile, then recrystallised from acetone to give 1-(1,2,3,4-tetrahydronaphth-1-yl)cyclopropanecarbonitrile (8.3 g), mp 91°-93° C. was heated under gentle reflux for 2 hours The solvent was removed in vacuo then extracted with ethyl acetate (4×100 ml) The combined extracts were dried over magnesium sulphate the solvent removed in vacuo to leave a semi-solid which was filtered washed with acetonitrile recrystallised from acetone

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

Procedure: Cyclopropanecarbonitrile (17.14 g) was added dropwise to a mixture of lithium diisopropylamide solution (2M in a mixture of heptane, tetrahydrofuran and ethylbenzene; 128 ml), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (30 ml) and tetrahydrofuran (240 ml) stirring at -78° C. under nitrogen. Stirring was continued for 1 hour at this temperature then a solution of 1-chlorotetralin (48.4 g) in tetrahydrofuran (50 ml) was added slowly and after a further hour the solution was allowed to warm to ambient temperature, then was heated under gentle reflux for 2 hours. The solvent was removed in vacuo and the residue acidified with concentrated hydrochloric acid then extracted with ethyl acetate (4×100 ml). The combined extracts were dried over magnesium sulphate and the solvent removed in vacuo to leave a semi-solid which was filtered and washed with acetonitrile, then recrystallised from acetone to give 1-(1,2,3,4-tetrahydronaphth-1-yl)cyclopropanecarbonitrile (8.3 g), mp 91°-93° C. was heated under gentle reflux for 2 hours The solvent was removed in vacuo then extracted with ethyl acetate (4×100 ml) The combined extracts were dried over magnesium sulphate the solvent removed in vacuo to leave a semi-solid which was filtered washed with acetonitrile recrystallised from acetone

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

Procedure: Cyclopropanecarbonitrile (17.14 g) was added dropwise to a mixture of lithium diisopropylamide solution (2M in a mixture of heptane, tetrahydrofuran and ethylbenzene; 128 ml), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (30 ml) and tetrahydrofuran (240 ml) stirring at -78° C. under nitrogen. Stirring was continued for 1 hour at this temperature then a solution of 1-chlorotetralin (48.4 g) in tetrahydrofuran (50 ml) was added slowly and after a further hour the solution was allowed to warm to ambient temperature, then was heated under gentle reflux for 2 hours. The solvent was removed in vacuo and the residue acidified with concentrated hydrochloric acid then extracted with ethyl acetate (4×100 ml). The combined extracts were dried over magnesium sulphate and the solvent removed in vacuo to leave a semi-solid which was filtered and washed with acetonitrile, then recrystallised from acetone to give 1-(1,2,3,4-tetrahydronaphth-1-yl)cyclopropanecarbonitrile (8.3 g), mp 91°-93° C. was heated under gentle reflux for 2 hours The solvent was removed in vacuo then extracted with ethyl acetate (4×100 ml) The combined extracts were dried over magnesium sulphate the solvent removed in vacuo to leave a semi-solid which was filtered washed with acetonitrile recrystallised from acetone

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

Procedure: The method of example 6 was repeated (at 400° C. only) using 1:10 chloronaphthalene to DHP weight ratio. Conversion was 6% with 71% selectivity to naphthalene and 29% chlorotetralin. No tetralin was produced. at 400° C.

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

Procedure: The method of example 6 was repeated (at 400° C. only) using 1:10 chloronaphthalene to DHP weight ratio. Conversion was 6% with 71% selectivity to naphthalene and 29% chlorotetralin. No tetralin was produced. at 400° C.

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

Procedure: A 1 liter 3-necked flask equipped with a condenser, electronic thermocouple, mechanical stirrer and under a nitrogen atmosphere was charged with 1,2,3,4-tetrahydro-1-naphthol (34.3 g; 0.23 mol) in dry diethyl ether (420 ml). Pyridine (4.7 ml) was added and the flask was cooled to 16° C. in a bath of water and ice. A solution of thionyl chloride (50.7 ml; 0.70 mol) in ether (140 ml) was then added dropwise in 25 minutes and stirring continued overnight while allowing the bath to warm to ambient temperature. The reaction mixture was then poured into cold brine (400 g ice and 800 ml brine) and the organic phase was separated. The aqueous phase was extracted with diethyl ether (2×150 ml) and the combined organic extract was dried with sodium sulphate. Filtration and removal of solvent in vacuo gave 1,2,3,4-tetrahydro-1-chloronaphthalene (36.9 g) as an oil. This material was used without further purification. A 1 liter 3-necked flask equipped with a condenser the organic phase was separated The aqueous phase was extracted with diethyl ether (2×150 ml) the combined organic extract was dried with sodium sulphate Filtration and removal of solvent in vacuo