2-chlorotricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaene

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

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

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

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

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

Procedure: 5-Chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (6.86 g, 0.030 mol) and thiourea (2.28 g, 0.030 mol) were dissolved in ethanol (50 ml) and heated at reflux temperature for 2.5 h. After cooling to room temperature, 2 N sodium hydroxide (20 ml) was added and the mixture was subsequently heated to reflux temperature under a nitrogen atmosphere for 2 h. The reaction mixture was cooled to room temperature, made acidic by addition of a slight excess of sulfuric acid and extracted with diethyl ether (50 ml). The organic phase was washed with water (50 ml) and brine (30 ml). Evaporation in vacuo afforded 6.78 g (100%) of 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-thiol as an oil . The crude product was directly used in the next step without further purification. heated at reflux temperature for 2.5 h the mixture was subsequently heated to reflux temperature under a nitrogen atmosphere for 2 h The reaction mixture was cooled to room temperature extracted with diethyl ether (50 ml) The organic phase was washed with water (50 ml) and brine (30 ml) Evaporation in vacuo

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

Procedure: Ethyl N-(diphenylmethylene)glycinate (12 g, 45 mmol) and 5-chlorodibenzosuberane (12.32 g, 54 mmol) are dissolved in 250 mL of dichloromethane, tetrabutylammonium bromide (17.6 g, 55 mmol) and 47 mL of 50% sodium hydroxide solution are added and the mixture is mechanically stirred at room temperature for 4 hours. Then it is diluted with 75 mL of dichloromethane and water and the layers are separated. The organic layer is washed with water, dried over magnesium sulfate, filtered, and stripped under vacuum to give a brown orange oil. The oil is taken up in 250 mL of diethyl ether and 100 mL of water. The diethyl ether solution is additionally washed with water, dried (magnesium sulfate), and stripped to give a clear red-orange sticky oil residue (~21 g) which is used in the next step without purification. the layers are separated The organic layer is washed with water dried over magnesium sulfate filtered to give a brown orange oil The diethyl ether solution is additionally washed with water dried (magnesium sulfate)

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

Procedure: Ethyl N-(diphenylmethylene)glycinate (12 g, 45 mmol) and 5-chlorodibenzosuberane (12.32 g, 54 mmol) are dissolved in 250 mL of dichloromethane, tetrabutylammonium bromide (17.6 g, 55 mmol) and 47 mL of 50% sodium hydroxide solution are added and the mixture is mechanically stirred at room temperature for 4 hours. Then it is diluted with 75 mL of dichloromethane and water and the layers are separated. The organic layer is washed with water, dried over magnesium sulfate, filtered, and stripped under vacuum to give a brown orange oil. The oil is taken up in 250 mL of diethyl ether and 100 mL of water. The diethyl ether solution is additionally washed with water, dried (magnesium sulfate), and stripped to give a clear red-orange sticky oil residue (~21 g) which is used in the next step without purification. the layers are separated The organic layer is washed with water dried over magnesium sulfate filtered to give a brown orange oil The diethyl ether solution is additionally washed with water dried (magnesium sulfate)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 7.338 g (41.31 mol) of guvacoline hydrochloride (Arzneim. Forsch. 1989, 39(5), 539. ) in dioxane (100 ml) was added 5-chloro-dibenzosuberane (14.933 g, 65.39 mmol), Nal (catalytic, ˜1 g), and triethylamine (17 mL, 122.0 mmol) to give a brown heterogeneous slurry that was heated at 90° C. overnight. The solvent was then concentrated and the resultant sludge was taken up in ethyl acetate and sequentially washed with Na2HPO4 buffer (pH 4), Na2CO3 (saturated aqueous), and brine. The organics were then dried over Na2SO4 and concentrated, resulting in a brown solid which was purified by chromatography on silica gel eluting with 1-5% ethyl acetate/hexanes to give 1-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester as a white solid (9.584 g, 28.74 mmol, 67%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 2.22 (dt, J=9.28, 2.68 Hz, 2H) 2.41 (t, J=5.56 Hz, 2H) 2.73-2.83 (m, 2H) 2.99-3.05 (m, 2H) 3.65 (s, 3 H) 3.90-4.00 (m, 2H) 4.11 (s, 1H) 6.94-6.99 (m, J=3.98, 3.98, 1.89, 1.77 Hz, 1 H) 7.05-7.11 (m, 4H) 7.13-7.21 (m, 4H). to give a brown heterogeneous slurry that The solvent was then concentrated sequentially washed with Na2HPO4 buffer (pH 4), Na2CO3 (saturated aqueous), and brine The organics were then dried over Na2SO4 concentrated resulting in a brown solid which was purified by chromatography on silica gel eluting with 1-5% ethyl acetate/hexanes

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 1,2,5,6-tetrahydropyridine-3-carboxylate hydrochloride (crude, 150 mmol), 5-chlorodibenzosuberane (41 g, 180 mmol, 1.2 eq), sodium iodide (2.2 g, 15 mmol, 0.1 eq) and triethylamine (63 mL, 450 mmol, 3.0 eq) in dioxane (300 mL) was stirred at 90° C. overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over MgSO4, and concentrated. The crude product was passed through a silica gel plug, eluting with CH2Cl2. After concentration, the resulting solid was triturated with ether to yield 27 g (55%) of methyl 1-(10,11-dihydro5H-dibenzo[a,d][7]annulen-5-yl)-1,2,5,6-tetrahydropyridine-3-carboxylate. The reaction mixture was concentrated in vacuo the residue was partitioned between ethyl acetate and water The organic phase was washed with brine dried over MgSO4 concentrated eluting with CH2Cl2 After concentration the resulting solid was triturated with ether

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

Procedure: 5-Chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (6.86 g, 0.030 mol) and thiourea (2.28 g, 0.030 mol) were dissolved in ethanol (50 ml) and heated at reflux temperature for 2.5 h. After cooling to room temperature, 2 N sodium hydroxide (20 ml) was added and the mixture was subsequently heated to reflux temperature under a nitrogen atmosphere for 2 h. The reaction mixture was cooled to room temperature, made acidic by addition of a slight excess of sulfuric acid and extracted with diethyl ether (50 ml). The organic phase was washed with water (50 ml) and brine (30 ml). Evaporation in vacuo afforded 6.78 g (100%) of 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-thiol as an oil . The crude product was directly used in the next step without further purification. heated at reflux temperature for 2.5 h the mixture was subsequently heated to reflux temperature under a nitrogen atmosphere for 2 h The reaction mixture was cooled to room temperature extracted with diethyl ether (50 ml) The organic phase was washed with water (50 ml) and brine (30 ml) Evaporation in vacuo

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

Procedure: 5-Chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (6.86 g, 0.030 mol) and thiourea (2.28 g, 0.030 mol) were dissolved in ethanol (50 ml) and heated at reflux temperature for 2.5 h. After cooling to room temperature, 2 N sodium hydroxide (20 ml) was added and the mixture was subsequently heated to reflux temperature under a nitrogen atmosphere for 2 h. The reaction mixture was cooled to room temperature, made acidic by addition of a slight excess of sulfuric acid and extracted with diethyl ether (50 ml). The organic phase was washed with water (50 ml) and brine (30 ml). Evaporation in vacuo afforded 6.78 g (100%) of 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-thiol as an oil . The crude product was directly used in the next step without further purification. heated at reflux temperature for 2.5 h the mixture was subsequently heated to reflux temperature under a nitrogen atmosphere for 2 h The reaction mixture was cooled to room temperature extracted with diethyl ether (50 ml) The organic phase was washed with water (50 ml) and brine (30 ml) Evaporation in vacuo

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

Procedure: Ethyl N-(diphenylmethylene)glycinate (12 g, 45 mmol) and 5-chlorodibenzosuberane (12.32 g, 54 mmol) are dissolved in 250 mL of dichloromethane, tetrabutylammonium bromide (17.6 g, 55 mmol) and 47 mL of 50% sodium hydroxide solution are added and the mixture is mechanically stirred at room temperature for 4 hours. Then it is diluted with 75 mL of dichloromethane and water and the layers are separated. The organic layer is washed with water, dried over magnesium sulfate, filtered, and stripped under vacuum to give a brown orange oil. The oil is taken up in 250 mL of diethyl ether and 100 mL of water. The diethyl ether solution is additionally washed with water, dried (magnesium sulfate), and stripped to give a clear red-orange sticky oil residue (~21 g) which is used in the next step without purification. the layers are separated The organic layer is washed with water dried over magnesium sulfate filtered to give a brown orange oil The diethyl ether solution is additionally washed with water dried (magnesium sulfate)